CN100371334C - Method for preparing (S)-3-hydroxy group-gamma-butyrolactone - Google Patents
Method for preparing (S)-3-hydroxy group-gamma-butyrolactone Download PDFInfo
- Publication number
- CN100371334C CN100371334C CNB2005100653831A CN200510065383A CN100371334C CN 100371334 C CN100371334 C CN 100371334C CN B2005100653831 A CNB2005100653831 A CN B2005100653831A CN 200510065383 A CN200510065383 A CN 200510065383A CN 100371334 C CN100371334 C CN 100371334C
- Authority
- CN
- China
- Prior art keywords
- butyrolactone
- gamma
- hydroxyl
- preparation
- sulfonyloxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a method for preparing (S)-3-hydroxy group-gamma-butyrolactone, relates to an intermediate body of chiral drugs and provides a synthetic method for (S)-3-hydroxy-gamma-butyrolactone (4). The synthetic method has the advantages of cheap raw material, simple technology and high yield. (2R, 3R)-2, 3-dihydroxy-gamma-butyrolactone (1) is dissolved in dichloromethane, and an organic alkali acid-binding agent is dropped in the mixture after cooling to 0 DEG C. Sulfonylation reagent is added, and solid is removed by filtration. The (2R, 3R)-2-sulfonyloxy-3-hydroxy-gamma-butyrolactone (2) is obtained after the solvent is distilled out. (2R, 3R)-2-sulfonyloxy-3-hydroxy-gamma-butyrolactone (2) is dissolved in an organic solvent and added with alkali halide, and ethyl acetate is added for extraction after the solvent is distilled out. (2R, 3R)-2-sulfonyloxy-3-hydroxy-gamma-butyrolactone (3) is obtained after the solvent is decompressed and distilled out. The (2R, 3R)-2-sulfonyloxy-3-hydroxy-gamma-butyrolactone (3) is dissolved in an organic solvent and added with a dehalogenation catalyst, and the solvent is distilled out by decompression after solid is filtered. Products can be obtained by column chromatography or underpressure distillation and purification.
Description
Technical field
The present invention relates to a kind of chiral drug intermediate, especially relate to the preparation method of a kind of multiduty chiral drug intermediate (S)-3-hydroxyl-gamma-butyrolactone.
Background technology
(S)-3-hydroxyl-gamma-butyrolactone (4) is a kind of multiduty chiral drug intermediate, is widely used in the synthetic of his spit of fland fat-reducing medicament of asymmetric synthesis and several.The synthetic method of existing (S)-3-hydroxyl-gamma-butyrolactone mainly contains:
1) with the L MALIC ACID is raw material, by the method for esterification, selective reduction and cyclisation.Though this method route is short, productive rate is higher, the complex compound that adopts borine and dimethyl sulphide in the reaction needs the anhydrous and oxygen-free condition as reductive agent; Simultaneously, borine dimethyl sulphide complex compound is not only very expensive, and toxicity is very big, so this route is dangerous big, is difficult to preparation (S)-3-hydroxyl-gamma-butyrolactone on technical scale.Although done improvement afterwards, use sodium borohydride-lithium chloride as reductive agent, its industrialized cost is still very high;
2) with the oligose be the alkaline oxygenated method that raw material passes through hydrogen peroxide.
This method is carried out oxidation scission with hydrogen peroxide with lactose, maltose, Star Dri 5 and starch and is formed (3S)-3 under alkaline condition, 4-dihydroxyl butyric acid, and further under acidic conditions cyclisation obtain (S)-3-hydroxyl-gamma-butyrolactone.Though the cost of this method raw material is low, yield also medium (being about 60%), in actually operating, because the concentration of reaction raw materials is low, by product is many, and need remove a large amount of water, extremely during energy charge, therefore the industrialization of this method is still had any problem.
Summary of the invention
The present invention aims to provide the preparation method of a kind of raw material cheapness, technology is simple, yield is high (S)-3-hydroxyl-gamma-butyrolactone (4).
Reaction equation of the present invention is as follows:
Concrete steps of the present invention are as follows:
1), (2R, 3R)-preparation of 2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2)
With (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, make the solution of 0.1～0.5 mol, after being cooled to 0 ℃ with ice-water bath, be added dropwise to and be equivalent to (2R, 3R)-2, a kind of organic base acid-capture agent of (1) 0.9～1.8 times of molar weight of 3-dihydroxyl-gamma-butyrolactone adds and is equivalent to (2R, 3R)-2, the sulfonylation agent of (1) 0.9～1.4 times of molar weight of 3-dihydroxyl-gamma-butyrolactone is complete to feedstock conversion, and solids removed by filtration obtains (2R after steaming desolventizes, 3R)-and 2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) crude product, be directly used in next step reaction;
2), (2S, 3R)-preparation of 2 halogen-3-hydroxyl-gamma-butyrolactone (3)
With above-mentioned (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the organic solvent, make the solution of 0.8～2.0 mol, add again and be equivalent to (2R, 3R)-alkali metal halide of 2-sulfonyloxy-(2) 0.9～1.5 times of molar weights of 3-hydroxyl-gamma-butyrolactone, reaction mixture under refluxad finishes to feedstock conversion, after boiling off solvent, the adding quality is (2R, 3R)-ethyl acetate extraction of (2) 30～50 times of 2-sulfonyloxies-3-hydroxyl-gamma-butyrolactone 2～3 times, remove under reduced pressure gained behind the solvent (2S, 3R)-2-halo-3-hydroxyl-gamma-butyrolactone (3) crude product is directly used in next step reaction;
3), the preparation of (S) 3-hydroxyl-gamma-butyrolactone (4)
With above-mentioned product (2S, 3R)-2-halo-3-hydroxyl-gamma-butyrolactone (3) is dissolved in the organic solvent, make the solution of 0.5～1.2 mol, add then and be equivalent to (2S, 3R)-dehalogenate activator of 2-halo-3-hydroxyl-gamma-butyrolactone (3) 0.5%～10% molar weights, reaction mixture is at the hydrogen pressure of 100～500kPa, complete in 20～80 ℃ to raw material reaction, behind the elimination solid, the pressure reducing and steaming solvent, through column chromatography or underpressure distillation purifying, get (S)-3-hydroxyl-gamma-butyrolactone (4) again.
In step 1), with (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, makes the solution of 0.2～0.3 mol.After being cooled to 0 ℃ with ice-water bath, be added dropwise to and be equivalent to (2R, 3R)-2, a kind of organic base acid-capture agent of (1) 1.1～1.5 times of molar weight of 3-dihydroxyl-gamma-butyrolactone, said organic base acid-capture agent is selected from tertiary amine or the pyridine that alkyl carbon chain is C1～C3, tertiary amine or the pyridine of preferred C2～C3; Add again and be equivalent to (2R; 3R)-2; the sulfonylation agent of (1) 1.0～1.2 times of molar weight of 3-dihydroxyl-gamma-butyrolactone; said sulfonylation agent is selected from alkyl sulfonyl chloride, aryl sulfonyl chloride, perfluorinated sulfonic acid acid anhydride or the sulfur oxychloride of C1～C3, alkyl sulfonyl chloride or the aryl sulfonyl chloride of preferred C1～C2.
In step 2) in, with above-mentioned (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the organic solvent, make the solution of 1.0～1.5 mol, said organic solvent is selected from the organic acid of polar C1～C2, alcohol, dimethyl formamide or methyl-sulphoxide etc., organic acid or the alcohol of preferred C1～C2, add again and be equivalent to (2R, 3R)-alkali metal halide of 2-sulfonyloxy-(2) 1.0～1.3 times of molar weights of 3-hydroxyl-gamma-butyrolactone, said alkali metal halide is selected from lithium, the chlorine of sodium and potassium, the bromine or iodine thing, the bromine or iodine thing of preferred lithium and potassium.
In step 3), with above-mentioned product (2S, 3R)-2 halogen-3-hydroxyl-gamma-butyrolactone (3) is dissolved in the organic solvent, makes the solution of 0.8～1.0 mol.Said organic solvent is selected from the organic acid of polar C1～C3 or alcohol etc., organic acid or the alcohol of preferred C1～C2, add then and be equivalent to (2S, 3R)-dehalogenate activator of 2 halogen-3-hydroxyl-gamma-butyrolactone (3) 0.8%～5% molar weights, said dehalogenate activator is selected from the dispersion thing of nickel, palladium, platinum or lawrencium metal and oxide compound thereof, the dispersion thing of preferred nickel or metallic palladium and oxide compound thereof, reaction mixture is at the hydrogen pressure of 200～400kPa, and is complete to raw material reaction in 30～60 ℃.
(the 2R that the present invention obtains with the isoascorbic acid from cheapness; 3R)-3-dihydroxyl-gamma-butyrolactone (1) is a raw material; form (2R by the selectivity sulfonylation; 3R)-2-sulphur acyloxy-3-hydroxyl-gamma-butyrolactone (2); it further replaces with metal halide, obtain product (2S, 3R)-2-halo-3-hydroxyl-gamma-butyrolactone (3); carry out three reactions steps of catalytic hydrogenolysis dehalogenation at last, obtain (S)-3-hydroxyl-gamma-butyrolactone.This synthetic method mild condition, yield height, intermediate need not to separate, easy handling, and the optical purity height of product is a kind of convenience, economy, the method for synthetic (S)-3-hydroxyl-gamma-butyrolactone efficiently.
Embodiment
Embodiment 1
Prepare (2R earlier, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2), with (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, make the solution of 0.1 mol, be cooled to 0 ℃ with ice-water bath after, stir and to be added dropwise to the triethylamine that is equivalent to (1) 1.3 times of molar weight down; Add the sulfur oxychloride that is equivalent to (1) 1.1 times of molar weight again, it is complete that mixture is stirred to feedstock conversion, solids removed by filtration, after desolventizing, steaming obtains (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone Asia (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) crude product, be directly used in next step reaction.
With above-mentioned (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the methyl alcohol, make the solution of 1.4 mol, add again and be equivalent to (2R, 3R)-lithium chloride of 2-sulfonyloxy-(2) 1.1 times of molar weights of 3-hydroxyl-gamma-butyrolactone, reaction mixture under refluxad is stirred to feedstock conversion and finishes, after boiling off solvent, the adding quality is (2R, 3R)-ethyl acetate extraction of (2) 50 times of 2-sulfonyloxies-3-hydroxyl-gamma-butyrolactone 2 times, (2S 3R)-(X=Cl) crude product of 2-chloro-3-hydroxyl-gamma-butyrolactone (3), is directly used in next step reaction to remove gained behind the solvent under reduced pressure.
Above-mentioned product (3) is dissolved in the methyl alcohol, make the solution of 0.6 mol, the dispersion thing that adds the nickel that is equivalent to (3) 5% molar weights then, reaction mixture is under the hydrogen pressure of 200kPa, and it is complete to be stirred to raw material reaction in 25 ℃, behind the elimination solid, the pressure reducing and steaming solvent, through column chromatography or underpressure distillation purifying, get (S)-3-hydroxyl-gamma-butyrolactone (4), productive rate 30%～85% again.[α]
D 20:-83.4 (c1.0, ethanol);
1HNMR (500MHZ, CDCl
3): δ (ppm): 2.499 (J 18.0 for d, 1H), 2.733 (dd, 1H, J18.0 and 6.0Hz), 3.517 (s, 1H), 4.289 (d, 1H, J10.0Hz), 4.401 (dd, 1H, J10.0 and 4.0Hz), 4.654 (m, 1H):
13CNMR (125MHZ, CDCl
3): δ (ppm): 177.6,76.7,67.6,37.9.
Embodiment 2
Similar to Example 1, its difference is first preparation (2S, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2), with (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, makes the solution of 0.25 mol, after being cooled to 0 ℃ with ice-water bath, stirring and be added dropwise to the diisopropyl ethyl amine that is equivalent to (1) 1.2 times of molar weight down; Add the methylsulfonyl chloride that is equivalent to (1) 1.2 times of molar weight again, it is complete that mixture is stirred to feedstock conversion, solids removed by filtration, obtain after steaming desolventizes (2S, 3R)-2-mesyloxy-3-hydroxyl-gamma-butyrolactone (2) crude product, be directly used in next step reaction.
With above-mentioned (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the formic acid, make the solution of 1.5 mol, add again and be equivalent to (2R, 3R)-lithiumbromide of 2-sulfonyloxy-(2) 1.0 times of molar weights of 3-hydroxyl-gamma-butyrolactone, reaction mixture under refluxad is stirred to feedstock conversion and finishes, after boiling off solvent, the adding quality is (2R, 3R)-ethyl acetate extraction of 45 times of 2-sulfonyloxies-3-hydroxyl-gamma-butyrolactone 2 times, (2S 3R)-(X=Br) crude product of 2-bromo-3-hydroxyl-gamma-butyrolactone (3), is directly used in next step reaction to remove gained behind the solvent under reduced pressure.
Above-mentioned product (3) is dissolved in the ethanol, make the solution of 0.8 mol, the dispersion thing that adds the palladium that is equivalent to (3) 3% molar weights then, reaction mixture is under the hydrogen pressure of 250kPa, it is complete to be stirred to raw material reaction in 30 ℃, behind the elimination solid, and the pressure reducing and steaming solvent, through column chromatography or underpressure distillation purifying, get (S)-3-hydroxyl-gamma-butyrolactone (4) again.
Embodiment 3
Similar to Example 1, its difference is first preparation (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2), with (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, makes the solution of 0.3 mol, after being cooled to 0 ℃ with ice-water bath, stirring and be added dropwise to the pyridine that is equivalent to (1) 1.4 times of molar weight down; Add three fluorosulfonic anhydride that are equivalent to (1) 1.4 times of molar weight again, it is complete that mixture is stirred to feedstock conversion, and solids removed by filtration obtains (2S after steaming desolventizes, 3R)-and 2-trifluoro-methanesulfonyl oxy-3-hydroxyl-gamma-butyrolactone (2) crude product, be directly used in next step reaction.
With above-mentioned (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the acetate, make the solution of 1.3 mol, add again and be equivalent to (2R, 3R)-lithium iodide of 2-sulfonyloxy-(2) 1.3 times of molar weights of 3-hydroxyl-gamma-butyrolactone, reaction mixture under refluxad is stirred to feedstock conversion and finishes, after boiling off solvent, the adding quality is (2R, 3R)-ethyl acetate extraction of 40 times of 2-sulfonyloxies-3-hydroxyl-gamma-butyrolactone 2 times, (2S 3R)-(X=I) crude product of 2-iodo-3-hydroxyl-gamma-butyrolactone (3), is directly used in next step reaction to remove gained behind the solvent under reduced pressure.
Above-mentioned product (3) is dissolved in the formic acid, make the solution of 0.9 mol, the dispersion thing that adds the nickel that is equivalent to (3) 8% molar weights then, reaction mixture is under the hydrogen pressure of 400kPa, it is complete to be stirred to raw material reaction in 50 ℃, behind the elimination solid, and the pressure reducing and steaming solvent, through column chromatography or underpressure distillation purifying, get (S)-3-hydroxyl-gamma-butyrolactone (4) again.
Embodiment 4
Similar to Example 1, its difference is first preparation (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2), with (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, makes the solution of 0.35 mol, after being cooled to 0 ℃ with ice-water bath, stirring and be added dropwise to the diisopropyl ethyl amine that is equivalent to (1) 1.0 times of molar weight down; Add the methylsulfonyl chloride that is equivalent to (1) 1.4 times of molar weight again, it is complete that mixture is stirred to feedstock conversion, solids removed by filtration, obtain after steaming desolventizes (2S, 3R)-2-mesyloxy-3-hydroxyl-gamma-butyrolactone (2) crude product, be directly used in next step reaction.
With above-mentioned (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the Virahol, make the solution of 0.8 mol, add again and be equivalent to (2R, 3R)-Potassium Bromide of 2-sulfonyloxy-(2) 1.2 times of molar weights of 3-hydroxyl-gamma-butyrolactone, reaction mixture under refluxad is stirred to feedstock conversion and finishes, after boiling off solvent, the adding quality is (2R, 3R)-ethyl acetate extraction of 35 times of 2-sulfonyloxies-3-hydroxyl-gamma-butyrolactone 2 times, (2S 3R)-(X=Br) crude product of 2-bromo-3-hydroxyl-gamma-butyrolactone (3), is directly used in next step reaction to remove gained behind the solvent under reduced pressure.
Above-mentioned product (3) is dissolved in the acetate, make the solution of 1.0 mol, the dispersion thing that adds the platinum oxide that is equivalent to (3) 0.5% molar weights then, reaction mixture is under the hydrogen pressure of 500kPa, it is complete to be stirred to raw material reaction in 40 ℃, behind the elimination solid, and the pressure reducing and steaming solvent, through column chromatography or underpressure distillation purifying, get (S)-3-hydroxyl-gamma-butyrolactone (4) again.
Embodiment 5
Similar to Example 1, its difference is first preparation (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2), with (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, makes the solution of 0.4 mol, after being cooled to 0 ℃ with ice-water bath, stirring and be added dropwise to the triethylamine that is equivalent to (1) 1.6 times of molar weight down; Add the Tosyl chloride that is equivalent to (1) 0.9 times of molar weight again, it is complete that mixture is stirred to feedstock conversion, and solids removed by filtration obtains (2S after steaming desolventizes, 3R)-and 2-tolysulfonyl oxygen base-3-hydroxyl-gamma-butyrolactone (2) crude product, be directly used in next step reaction.
With above-mentioned (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the dimethyl formamide, make the solution of 1.6 mol, add again and be equivalent to (2R, 3R)-potassiumiodide of 2-sulfonyloxy-(2) 0.9 times of molar weights of 3-hydroxyl-gamma-butyrolactone, reaction mixture under refluxad is stirred to feedstock conversion and finishes, after boiling off solvent, the adding quality is (2R, 3R)-ethyl acetate extraction of 30 times of 2-sulfonyloxies-3-hydroxyl-gamma-butyrolactone 2 times, (2S 3R)-(X=I) crude product of 2-iodo-3-hydroxyl-gamma-butyrolactone (3), is directly used in next step reaction to remove gained behind the solvent under reduced pressure.
Above-mentioned product (3) is dissolved in the methyl alcohol, make the solution of 1.2 mol, the dispersion thing that adds the lawrencium that is equivalent to (3) 10% molar weights then, reaction mixture is under the hydrogen pressure of 450kPa, it is complete to be stirred to raw material reaction in 60 ℃, behind the elimination solid, and the pressure reducing and steaming solvent, through column chromatography or underpressure distillation purifying, get (S)-3-hydroxyl-gamma-butyrolactone (4) again.
Claims (10)
1. the preparation method of (S)-3-hydroxyl-gamma-butyrolactone is characterized in that its reaction equation is as follows:
Concrete steps are:
1), (2R, 3R)-preparation of 2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2)
With (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, make the solution of 0.1～0.5 mol, after being cooled to 0 ℃ with ice-water bath, be added dropwise to and be equivalent to (2R, 3R)-2, a kind of organic base acid-capture agent of (1) 0.9～1.8 times of molar weight of 3-dihydroxyl-gamma-butyrolactone adds and is equivalent to (2R, 3R)-2, the sulfonylation agent of (1) 0.9～1.4 times of molar weight of 3-dihydroxyl-gamma-butyrolactone is complete to feedstock conversion, and solids removed by filtration obtains (2R after steaming desolventizes, 3R)-and 2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) crude product, be directly used in next step reaction;
2), (2S, 3R)-preparation of 2-halogen-3-hydroxyl-gamma-butyrolactone (3)
With (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the organic solvent, make the solution of 0.8～2.0 mol, add again and be equivalent to (2R, 3R)-alkali metal halide of 2-sulfonyloxy-(2) 0.9～1.5 times of molar weights of 3-hydroxyl-gamma-butyrolactone, reaction mixture under refluxad finishes to feedstock conversion, after boiling off solvent, the adding quality is (2R, 3R)-ethyl acetate extraction of (2) 30～50 times of 2-sulfonyloxies-3-hydroxyl-gamma-butyrolactone 2～3 times, remove under reduced pressure gained behind the solvent (2S, 3R)-2-halo-3-hydroxyl-gamma-butyrolactone (3) crude product is directly used in next step reaction;
3), the preparation of (S)-3-hydroxyl-gamma-butyrolactone (4)
With product (2S, 3R)-2-halo-3-hydroxyl-gamma-butyrolactone (3) is dissolved in the organic solvent, make the solution of 0.5～1.2 mol, add then and be equivalent to (2S, 3R)-dehalogenate activator of 2-halo-3-hydroxyl-gamma-butyrolactone (3) 0.5%～10% molar weights, reaction mixture is at the hydrogen pressure of 100～500kPa, complete in 20～80 ℃ to raw material reaction, behind the elimination solid, the pressure reducing and steaming solvent, through column chromatography or underpressure distillation purifying, get (S)-3-hydroxyl-gamma-butyrolactone (4) again.
2. the preparation method of (S)-3-hydroxyl-gamma-butyrolactone as claimed in claim 1, it is characterized in that in step 1), with (2R, 3R)-2,3-dihydroxyl-gamma-butyrolactone (1) is dissolved in the methylene dichloride, makes the solution of 0.2～0.3 mol, after being cooled to 0 ℃ with ice-water bath, be added dropwise to and be equivalent to (2R, 3R)-2, a kind of organic base acid-capture agent of (1) 1.1～1.5 times of molar weight of 3-dihydroxyl-gamma-butyrolactone.
3. the preparation method of (S)-3-hydroxyl-gamma-butyrolactone as claimed in claim 1 or 2 is characterized in that in step 1), and said organic base acid-capture agent is selected from tertiary amine or the pyridine that alkyl carbon chain is C1～C3.
4. the preparation method of (S)-3-hydroxyl-gamma-butyrolactone as claimed in claim 1 or 2; it is characterized in that in step 1), adding and be equivalent to (2R; 3R)-2; the sulfonylation agent of (1) 1.0～1.2 times of molar weight of 3-dihydroxyl-gamma-butyrolactone, said sulfonylation agent are selected from alkyl sulfonyl chloride, aryl sulfonyl chloride, perfluorinated sulfonic acid acid anhydride or the sulfur oxychloride of C1～C3.
5. the preparation method of (S)-3-hydroxyl-gamma-butyrolactone as claimed in claim 1, it is characterized in that in step 2) in, with (2R, 3R)-2-sulfonyloxy-3-hydroxyl-gamma-butyrolactone (2) is dissolved in the organic solvent, make the solution of 1.0～1.5 mol, said organic solvent is selected from organic acid, alcohol, dimethyl formamide or the methyl-sulphoxide of polar C1～C2.
6. as the preparation method of claim 1 or 5 described (S)-3-hydroxyl-gamma-butyrolactone, it is characterized in that adding and be equivalent to (2R, 3R)-and the alkali metal halide of 2-sulfonyloxy-(2) 1.0～1.3 times of molar weights of 3-hydroxyl-gamma-butyrolactone, said alkali metal halide is selected from chlorine, the bromine or iodine thing of lithium, sodium and potassium.
7. the preparation method of (S)-3-hydroxyl-gamma-butyrolactone as claimed in claim 1 is characterized in that in step 3), will (2S, 3R)-2-halogen-3-hydroxyl-gamma-butyrolactone (3) is dissolved in the organic solvent, makes the solution of 0.8～1.0 mol.
8. as the preparation method of claim 1 or 7 described (S)-3-hydroxyl-gamma-butyrolactone, it is characterized in that said organic solvent is selected from organic acid or the alcohol of polar C1～C3.
9. as the preparation method of claim 1 or 7 described (S)-3-hydroxyl-gamma-butyrolactone, it is characterized in that in step 3), add and be equivalent to (2S, 3R)-and the dehalogenate activator of 2-halogen-3-hydroxyl-gamma-butyrolactone (3) 0.8%～5% molar weights, said dehalogenate activator is selected from the dispersion thing of nickel, palladium, platinum or lawrencium metal and oxide compound thereof.
10. the preparation method of (S)-3-hydroxyl-gamma-butyrolactone as claimed in claim 1 is characterized in that in step 3), and reaction mixture is at the hydrogen pressure of 200～400kPa, and is complete to raw material reaction in 30～60 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100653831A CN100371334C (en) | 2005-04-12 | 2005-04-12 | Method for preparing (S)-3-hydroxy group-gamma-butyrolactone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100653831A CN100371334C (en) | 2005-04-12 | 2005-04-12 | Method for preparing (S)-3-hydroxy group-gamma-butyrolactone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1687046A CN1687046A (en) | 2005-10-26 |
| CN100371334C true CN100371334C (en) | 2008-02-27 |
Family
ID=35305088
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100653831A Expired - Fee Related CN100371334C (en) | 2005-04-12 | 2005-04-12 | Method for preparing (S)-3-hydroxy group-gamma-butyrolactone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100371334C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102702146A (en) * | 2012-05-31 | 2012-10-03 | 北京工商大学 | Method for preparing 2-nonylene-gamma-lactone simply, conveniently and practically |
| CN104130225B (en) * | 2014-08-18 | 2016-04-27 | 上海理工大学 | A kind of synthetic method of tetronic acid |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4855232A (en) * | 1988-02-09 | 1989-08-08 | Agency Of Industrial Science & Technology | Method for production of glucose by use of transglucosidase |
| US5183910A (en) * | 1990-05-03 | 1993-02-02 | Eli Lilly And Company | Process and intermediates for chiral epoxides |
| CN1319595A (en) * | 1996-11-20 | 2001-10-31 | 可乐丽股份有限公司 | Method for producing optically active 3-hydroxy-gamna-butyrolactone |
| JP2001302653A (en) * | 2000-04-28 | 2001-10-31 | Daicel Chem Ind Ltd | Method for producing lactone |
-
2005
- 2005-04-12 CN CNB2005100653831A patent/CN100371334C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4855232A (en) * | 1988-02-09 | 1989-08-08 | Agency Of Industrial Science & Technology | Method for production of glucose by use of transglucosidase |
| US5183910A (en) * | 1990-05-03 | 1993-02-02 | Eli Lilly And Company | Process and intermediates for chiral epoxides |
| CN1319595A (en) * | 1996-11-20 | 2001-10-31 | 可乐丽股份有限公司 | Method for producing optically active 3-hydroxy-gamna-butyrolactone |
| JP2001302653A (en) * | 2000-04-28 | 2001-10-31 | Daicel Chem Ind Ltd | Method for producing lactone |
Non-Patent Citations (3)
| Title |
|---|
| (S）-3-羟基内酯的合成. 章小波等.精细化工中间体，第35卷第3期. 2004 * |
| 2,3-isopropylidene -d-erythronolactone[furo[3,4-d]-1,3-dioxol-4(3aH)-one,dihydro-2,2-dimethyl-(3aR-cis-].. Cohen, Noal, et al.CA 105:6677,Vol.6 . 1999 * |
| A novel synthesis of (R)- and (S)- 4-hydrotetrahydrofuran-2-ones. Tanaka A, et al.Synthesis,Vol.6 . 1987 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1687046A (en) | 2005-10-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101619034B (en) | Diselenide compound synthesis method | |
| CN106349130B (en) | A kind of synthetic method of new Florfenicol | |
| CN100371334C (en) | Method for preparing (S)-3-hydroxy group-gamma-butyrolactone | |
| CN101054355B (en) | Compound of optically pure disulfenamides and application thereof | |
| Unsworth et al. | Rhodium (II)-catalysed tandem aziridination and ring-opening: stereoselective synthesis of functionalised tetrahydrofurans | |
| CN109535120B (en) | Preparation method of 7-substituted-3, 4,4, 7-tetrahydrocyclobutane coumarin-5-ketone | |
| CN106966889A (en) | One kind (E) β, γ alkene-carboxylic acid's derivatives and preparation method thereof | |
| CN109553595B (en) | Preparation method of chiral gamma-butyrolactone and intermediate thereof | |
| CN105732648A (en) | Nitrogen heterocyclic ring compound of pyrrolofuran and synthetic method | |
| CA2568800A1 (en) | Process for producing 3-aminomethyltetrahydrofuran derivative | |
| CN85108407A (en) | Hydroquinone derivative's preparation method | |
| CN105085563A (en) | Branched allyl compound, and preparation method and application thereof | |
| CN111793047B (en) | Preparation method of eribulin intermediate | |
| CN109265385B (en) | Synthesis process of chiral catalyst | |
| CN102356067B (en) | Method for producing 2,2 difluoroethylamine derivatives by imine hydrogenation | |
| CN102070633B (en) | Method for synthesizing 1,8-diazaspiro[4.5]decane with protective group | |
| CN112441998A (en) | Preparation method of eribulin intermediate | |
| CN104230880A (en) | Simple preparation method of 2-((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxyhexacyclo-4-yl)acetate | |
| CN115340446B (en) | Chiral benzocyclobutene alcohol, synthesis method and application thereof | |
| CN107445879B (en) | Preparation method of Latricinib intermediate | |
| WO2002072505A1 (en) | Optical resolver and method of optically resolving alcohol with the same | |
| CN111423405B (en) | Method for synthesizing benzopyran 3 alcohol derivative compound | |
| JP2012116775A (en) | Method for producing ecteinascidin | |
| CN110577483B (en) | Green synthesis method of 3, 3-disubstituted-2-indolone | |
| CN112939830B (en) | Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Longhai Bestally Biotechnology Co., Ltd. Assignor: Xiamen University Contract record no.: 2011350000276 Denomination of invention: Process for the preparation of (S) -3- hydroxy - gamma lactone Granted publication date: 20080227 License type: Exclusive License Open date: 20051026 Record date: 20111231 |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080227 Termination date: 20120412 |