CN106316886A - Cis form-3- (tert butoxycarbonylamino) naphthenic acid preparing method - Google Patents
Cis form-3- (tert butoxycarbonylamino) naphthenic acid preparing method Download PDFInfo
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- CN106316886A CN106316886A CN201610713615.8A CN201610713615A CN106316886A CN 106316886 A CN106316886 A CN 106316886A CN 201610713615 A CN201610713615 A CN 201610713615A CN 106316886 A CN106316886 A CN 106316886A
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- cis
- naphthenic acid
- butoxycarbonyl amino
- acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/08—Separation; Purification; Stabilisation; Use of additives
Abstract
The invention discloses a method for preparing cis form -3- (tert butoxycarbonylamino) naphthenic acid with the steps of putting m-aminobenzoic acid, catalysts and solvents into the high-pressure reaction kettle and obtaining cis-trans mixed m-aminonaphthenic acid through high-pressure hydrogenation; then putting the m-aminonaphthenic acid into the solvents, adding certain sodium alkoxide as the catalyst and obtaining the m-aminonaphthenic acid with the content exceeding 90% after temperature rise and backflow through isomerization reaction; protecting amidogen by BOC and finally obtaining pure cis form -3- (tert butoxycarbonylamino) naphthenic acid through dichloromethane and petroleum ether recrystallization. Beneficial effects of the invention: the invention provides a method for preparing the cis form -3- (tert butoxycarbonylamino) naphthenic acid with raw materials easy to get and for mass production and cost largely reduced.
Description
Technical field
The invention belongs to chemical field, be specifically related to a kind of cis-3-(t-butoxycarbonyl amino) system of naphthenic acid
Preparation Method.
Background technology
Cis-3-(t-butoxycarbonyl amino) preparation method of naphthenic acid, document report is seldom.It is typically to use dioxy
Change platinum and make catalyst, utilize gavaculine to do catalytic material hydrogenation, thus obtain the 3-aminocyclohexyl that cis-content is dominant
Alkane formic acid.Then protected by amino BOC, obtain the 3-(t-butoxycarbonyl amino of cis trans mixing) naphthenic acid.?
Afterwards by being repeatedly recrystallized to give pure cis-3-(t-butoxycarbonyl amino) naphthenic acid.The fatal defects of this method
It is, in order to obtain the 3-cyclohexane-carboxylic acid that cis-content is dominant, has used expensive platinum dioxide catalyst, and this
Planting catalyst can not recycled.And in order to obtain pure product, the method employing repeatedly recrystallization, cause yield very
Low, solvent usage amount is big.This method is not suitable for large-scale production.Cis-3-(t-butoxycarbonyl amino) naphthenic acid work
For a kind of medicine intermediate, being applied to the synthesis of many medicines, its importance is self-evident, accordingly, it would be desirable to one is suitable for
The preparation method of large-scale production.
Summary of the invention
In order to solve the problems referred to above, the invention provides the preparation method of trans-4-hydroxycyclohexanecarboxylate, concrete technology
Scheme is as follows:
Step one: by gavaculine, catalysts and solvents joins in autoclave, is passed through hydrogen, in High Temperature High Pressure
Under the conditions of, obtain 3-cyclohexane-carboxylic acid；
Step 2: join in solvent by 3-cyclohexane-carboxylic acid, adds appropriate sodium alkoxide, temperature rising reflux, after be down to room temperature,
Add appropriate water, dissolved solid, the acetone soln of dropping BOC2O.Stir 12 hours.Dilute hydrochloric acid adjusts pH value to be 2, filters,
To cis-3-(t-butoxycarbonyl amino) naphthenic acid crude product (content is more than 90%)；
Step 3: by cis-3-(t-butoxycarbonyl amino) naphthenic acid crude product, with a certain proportion of dichloromethane petroleum ether
Mixed solvent recrystallization, obtains pure cis-3-(t-butoxycarbonyl amino) naphthenic acid.
Preferably, the catalyst of hydrogenation is ruthenium Pd/carbon catalyst；Solvent is water；Reaction temperature is 80-150 degree；Reaction
Pressure is 1-3MPa.
Preferably, in isomerization reaction, solvent for use is in methanol, ethanol, propanol, n-butyl alcohol and the tert-butyl alcohol
Kind；Sodium alkoxide used is the one in Feldalat NM, Sodium ethylate, sodium propoxide and sodium tert-butoxide.
Preferably, the solvent used by recrystallization is the ratio of dichloromethane petroleum ether mixed solvent, dichloromethane and petroleum ether
Example is 5:1, the consumption (volume L) of mixed solvent and cis-3-(t-butoxycarbonyl amino) amount (quality of naphthenic acid crude product
Kg) ratio is 3:1 to 1:1.
Beneficial effects of the present invention: the invention provides a kind of cis-3-(t-butoxycarbonyl amino) naphthenic acid
Preparation method, raw material is easy to get, and can be with large-scale production, and cost is greatly reduced.
Accompanying drawing explanation
Fig. 1 is course of reaction figure in the present invention.
Detailed description of the invention
Embodiment
The preparation of 3-cyclohexane-carboxylic acid, in 50L autoclave, adds 10 kilograms of gavaculines, and 30 is public
Jin water, 0.3 kilogram of 10% ruthenium C catalyst, nitrogen replace once, hydrogen exchange three times.Open stirring, pressurized with hydrogen to 1MPa,
It is warming up to 100 degree, starts to inhale hydrogen, be progressively warming up to 120 degree, keep constant temperature till not inhaling hydrogen.Sampling monitoring, efficient liquid phase
Chromatograph (HPLC) is analyzed, and the reaction of raw material gavaculine is completely.Being down to room temperature, hydrogen of draining, nitrogen is replaced once.Filter out
Catalyst, is evaporated off the water in reactant liquor, obtains thick thing, adds 10L methanol, stirring to pulp, obtains dispersibility fine
White powder.Filtering, be dried, obtain 10 kilograms of 3-cyclohexane-carboxylic acid, cis-content is 70%.
Cis-3-(t-butoxycarbonyl amino) preparation of naphthenic acid crude product, by 10 kilograms of 3-cyclohexane-carboxylic acid,
30L methanol joins in 50L reactor, opens stirring, is dividedly in some parts 6 kilograms of Feldalat NMs.Being warming up to 60 degree, back flow reaction 3 is little
Time, it is cooled to 0 degree.In reactant liquor, drip the water of 5 kilograms, then drip the acetone soln of 12 kilograms of BOC2O, be stirred at room temperature
Night.10% dilute hydrochloric acid is 2 to PH.Solid filters, and dries, obtains 20 kilograms of Lycoperdon polymorphum Vitt powder, the most cis-3-(t-butoxycarbonyl amino)
Naphthenic acid crude product (containing 3% trans-3-(t-butoxycarbonyl amino) naphthenic acid).
Cis-3-(t-butoxycarbonyl amino) preparation of naphthenic acid fine work, 20 kilograms of trans-4-hydroxyl rings will be appealed
Hexane formic acid crude product, joins (dichloromethane: petroleum ether=5:1) in the mixed solvent of 40L dichloromethane and petroleum ether, heats up
To 50 degree, stirring 2 hours, system is molten clearly.Slow cooling, to 0 degree, is incubated 2 hours, separates out large quantities of white powder.Filter, dry
Dry, obtain 18 kilograms of cis-3-(t-butoxycarbonyl aminos) naphthenic acid, content 99%.
In the present embodiment, the raw material being easily easy to get by some, carry out series reaction, obtain highly purified mesh
Mark product, cost has obtained the biggest reduction, is suitable for large-scale production.
Claims (4)
1. cis-3-(t-butoxycarbonyl amino) preparation method of naphthenic acid, it specifically comprises the following steps that
Step one: by gavaculine, catalysts and solvents joins in autoclave, is passed through hydrogen, in High Temperature High Pressure
Under the conditions of, obtain 3-cyclohexane-carboxylic acid；
Step 2: join in solvent by 3-cyclohexane-carboxylic acid, adds appropriate sodium alkoxide, temperature rising reflux, after be down to 0 degree,
Add appropriate water dissolution solid, add BOC2O, obtain cis-3-(t-butoxycarbonyl amino) naphthenic acid crude product；
Step 3: by cis-3-(t-butoxycarbonyl amino) naphthenic acid crude product, with a certain proportion of dichloromethane petroleum ether
Mixed solvent recrystallization, obtains pure cis-3-(t-butoxycarbonyl amino) naphthenic acid.
2. according to the cis-3-(t-butoxycarbonyl amino of the one described in claim 1) preparation method of naphthenic acid, its
It is characterised by: the catalyst of hydrogenation is ruthenium Pd/carbon catalyst；Solvent is water；Reaction temperature is 80-150 degree；Reaction pressure is
1-3MPa。
3. according to the cis-3-(t-butoxycarbonyl amino of the one described in claim 1) preparation method of naphthenic acid, its
Being characterised by: in isomerization reaction, solvent for use is the one in methanol, ethanol, propanol, n-butyl alcohol and the tert-butyl alcohol；Used
Sodium alkoxide be the one in Feldalat NM, Sodium ethylate, sodium propoxide and sodium tert-butoxide.
4. according to the cis-3-(t-butoxycarbonyl amino of the one described in claim 1) preparation method of naphthenic acid, its
Being characterised by: the solvent used by recrystallization is dichloromethane petroleum ether mixed solvent, the ratio of dichloromethane and petroleum ether is 5:
1, the consumption (volume L) of mixed solvent and cis-3-(t-butoxycarbonyl amino) amount (quality kg) of naphthenic acid crude product
Ratio is 3:1 to 1:1.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610713615.8A CN106316886A (en) | 2016-08-24 | 2016-08-24 | Cis form-3- (tert butoxycarbonylamino) naphthenic acid preparing method |
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| CN201610713615.8A CN106316886A (en) | 2016-08-24 | 2016-08-24 | Cis form-3- (tert butoxycarbonylamino) naphthenic acid preparing method |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4754064A (en) * | 1983-10-24 | 1988-06-28 | Amoco Corporation | Preparation of cyclohexane dicarboxylic acids |
| CN102740847A (en) * | 2009-12-29 | 2012-10-17 | 阿维拉制药公司 | Heteroaryl compounds and uses thereof |
| WO2016037953A1 (en) * | 2014-09-08 | 2016-03-17 | Janssen Sciences Ireland Uc | Pyrrolopyrimidines for use in influenza virus infection |
-
2016
- 2016-08-24 CN CN201610713615.8A patent/CN106316886A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4754064A (en) * | 1983-10-24 | 1988-06-28 | Amoco Corporation | Preparation of cyclohexane dicarboxylic acids |
| CN102740847A (en) * | 2009-12-29 | 2012-10-17 | 阿维拉制药公司 | Heteroaryl compounds and uses thereof |
| WO2016037953A1 (en) * | 2014-09-08 | 2016-03-17 | Janssen Sciences Ireland Uc | Pyrrolopyrimidines for use in influenza virus infection |
Non-Patent Citations (2)
| Title |
|---|
| 孙国方等: "苯加氢制环己烷工艺及催化剂研究进展", 《工业催化》 * |
| 朱志庆: "对苯二甲酸催化加氢制1，4-环己烷二甲醇的专利技术", 《化工进展》 * |
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Application publication date: 20170111 |