WO2020051853A1 - 3,3-二取代氧化吲哚及其制备方法 - Google Patents

3,3-二取代氧化吲哚及其制备方法 Download PDF

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WO2020051853A1
WO2020051853A1 PCT/CN2018/105579 CN2018105579W WO2020051853A1 WO 2020051853 A1 WO2020051853 A1 WO 2020051853A1 CN 2018105579 W CN2018105579 W CN 2018105579W WO 2020051853 A1 WO2020051853 A1 WO 2020051853A1
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reaction
hydride
compound
palladium
active methylene
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French (fr)
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张士磊
毛玉健
刘晔
桂晶晶
陈韶华
胡延维
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南通纺织丝绸产业技术研究院
苏州大学
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
    • B01J31/28—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24 of the platinum group metals, iron group metals or copper
    • B01J31/30—Halides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin

Definitions

  • the invention belongs to the technical field of organic synthesis, and relates to the application of a metal hydride / palladium compound system in the reduction and one-pot reaction of an alkenyl active methylene compound, and particularly to a 3,3-disubstituted indole oxide and a preparation method thereof.
  • Sodium hydride is a strong base often used in laboratories and industries. For a long time, there have been few reports about its use as a reducing agent, and existing reactions require a large excess of reducing agent (3 equivalents), and at least 2 equivalents of sodium iodide are used as accelerators.
  • the reduction reaction of alkenyl active methylene compounds is generally carried out using hydrogen / palladium-carbon conditions; in addition, some hydrogen negative reagents, such as [(Ph 3 P) CuH] 6 (Stryker reagent), R 3 SiH, Hantzsch ester, etc. The reduction of this electron-deficient double bond can also be accomplished.
  • the technical problem to be solved by the present invention is to provide an application of a metal hydride / palladium compound system, so as to provide a method for reducing the preparation of 3,3-disubstituted indole oxide by active alkenyl methylene compound reduction.
  • the technical means for realizing the above-mentioned reduction of an alkenyl-active methylene compound is to use a metal hydride as a reducing agent, palladium and its salts as a catalyst, and react in a solvent to obtain a double bond reduced sodium salt product.
  • the electro reagent reacts to obtain a disubstituted product.
  • a method for preparing 3,3-disubstituted indole oxide using an alkenyl active methylene compound as a substrate, a metal hydride as a reducing agent, and a palladium compound as a catalyst, and reducing the reaction to obtain a reduced product; The reagent reacted to obtain 3,3-disubstituted indole.
  • R 1 and R 2 are independently selected from hydrogen, alkyl, phenyl, substituted phenyl, naphthyl, pyridyl, and quinolinyl.
  • the alkyl group may be a methyl group
  • the substituted phenyl group may be a halogen-substituted phenyl group or a methoxy-substituted phenyl group.
  • the metal hydride includes sodium hydride, lithium hydride, potassium hydride, calcium hydride, preferably sodium hydride, lithium hydride, and more preferably sodium hydride;
  • the palladium compound includes palladium chloride, palladium acetate, Pd (MeCN ) 2 Cl 2 , [( ⁇ 3 -C 3 H 5 ) PdCl] 2 , Pd (TFA) 2 , Pd (dppp) Cl 2 , Pd 2 (dba) 3 , Pd (C 6 H 5 CN) 2 Cl 2 , Pd (OH) 2 , Pd / C, Pd (PPh 3 ) 4 , Pd (PPh 3 ) 2 Cl 2 , preferably palladium chloride, palladium acetate, and more preferably palladium chloride.
  • the electrophile is benzyl bromide, methyl iodide, methyl acrylate or hydrogen peroxide.
  • the molar ratio of the palladium compound, metal hydride, and alkenyl active methylene compound is (0.01 to 1): (1 to 5): 1, preferably (0.03 to 0.1): (1 to 3 ): 1, more preferably 0.05: (1.5 to 2.5): 1, and most preferably 0.05: 2: 1.
  • the reaction is performed in a solvent under a nitrogen atmosphere;
  • the solvent includes DMA (N, N-dimethylacetamide), DMF, THF, DME or dioxane.
  • the temperature of the reduction reaction is -50 ° C to 120 ° C, preferably 0 to 50 ° C, and more preferably room temperature; the time of the reduction reaction is 0.3 to 10 hours, preferably 0.4 to 5 hours, and more preferably 0.5 hours.
  • the environment and temperature of the reaction between the reduction product and the electrophile are consistent with the reduction reaction.
  • the sodium hydride / palladium reduced alkenyl active methylene compound has the following advantages: 1) Compared with sodium borohydride, sodium hydride is cheaper (industrially, sodium borohydride is prepared from sodium hydride as a raw material); Compared with hydrogen / palladium carbon reduction, the sodium hydride method is safer; 2) sodium hydride has a small molecular weight and simple composition, and the amount used in the reaction is small, so using sodium hydride as a reducing agent is an atomic economic method; By-products except harmless sodium salt, no other waste is generated; 3) the product of the alkenyl active methylene compound reduced by sodium hydride is the sodium salt before the post-treatment, which is different from the existing reduction methods, Reactive sodium salts can continue to react with electrophilic reagents to obtain disubstituted products, which expands the application of alkenyl active methylene compounds. And in this one-pot reaction, the reducing and basic properties of sodium hydride are fully utilized, greatly improving the
  • the technical scheme of the present invention can be specifically described as follows: under the protection of nitrogen, palladium compound and metal hydride are suspended in a solvent and stirred, then a substrate alkenyl active methylene compound is added, and the reaction is performed at -50 ° C to 120 ° C for 0.3 -10 hours; add electrophilic reagents, continue the reaction until the reaction of the raw materials is complete, then add saturated ammonium chloride aqueous solution to stop the reaction, extract with solvent, evaporate to dryness, and purify by column chromatography to obtain the product.
  • the reduction of alkenyl active methylene compounds is a chemical reaction often used in organic synthesis.
  • two types of methods are used: one is hydrogen reduction with hydrogen / palladium carbon.
  • the use of hydrogen is a potential danger. Factors, improper operation will cause fire and explosion; the other is the use of reducing agents for reduction, which is expensive and requires treatment of a large amount of wastewater.
  • the present invention uses a relatively safe and inexpensive metal hydride instead of hydrogen and a reducing agent for the reduction of alkenyl active methylene compounds, and it is more important that this method fully utilizes the reducibility of sodium hydride And alkaline, you can perform a one-pot reaction.
  • the reduction system of the present invention is a simple method for reducing alkenyl active methylene compounds.
  • the hydride and palladium catalysts used are reagents easily available in the laboratory. Compared with commonly used hydrogen hydrogenation methods and reducing agent reduction methods, This method is easier to operate, has higher safety, mild conditions, high reaction yield, and can perform two-step reaction in one pot, and has high atomic economy and step economy. .

Abstract

提供了一种3,3-二取代氧化吲哚及其制备方法，反应包括以下步骤：以烯基活泼亚甲基化合物为底物、金属氢化物为还原剂、钯化合物为催化剂，还原反应，得到还原产物；以还原产物与亲电试剂反应，得到3,3-二取代氧化吲哚。所述方法是还原烯基活泼亚甲基化合物的简易方法，所用的氢化物和钯化合物催化剂都是实验室中容易获得的试剂，相比于常用的氢气氢化方法和还原剂还原方法，所述方法更易操作，安全性更高，条件温和，反应收率高，而且可以一锅两步反应，具有很高的原子经济性和步骤经济性。

Description

3,3-二取代氧化吲哚及其制备方法 技术领域
本发明属于有机合成技术领域，涉及金属氢化物/钯化合物体系在烯基活泼亚甲基化合物还原及一锅反应中的应用，具体涉及3,3-二取代氧化吲哚及其制备方法。
 背景技术
氢化钠是一种实验室及工业上经常使用的强碱，长期以来，很少有做为还原剂被使用的相关报道，而且现有反应需要大大过量的还原剂(3当量)，同时需要至少2当量的碘化钠做为促进剂。烯基活泼亚甲基化合物的还原反应一般是使用氢气/钯碳条件进行还原；另外，一些氢负试剂，比如[(Ph 3P)CuH] 6 (Stryker试剂)、R 3SiH、Hantzsch 酯等也可以完成这种缺电子双键的还原。但是，这些还原条件要么具有一定的危险性，比如易***的氢气；要么试剂较贵、反应缺乏原子经济性并且反应后需要处理较多的废弃物，比如[(Ph 3P)CuH] 6 (Stryker试剂)、R 3SiH、Hantzsch 酯等，或者有些反应后需要处理大量废水，所以在工业应用上也有一定的局限性。
技术问题
本发明要解决的技术问题是提供一种金属氢化物/钯化合物体系的应用，从而提供一种烯基活泼亚甲基化合物还原制备3,3-二取代氧化吲哚的方法。
 技术解决方案
本发明实现以上提及的还原烯基活泼亚甲基化合物的技术手段是以金属氢化物为还原剂，钯及其盐类为催化剂，在溶剂中反应得到双键还原的钠盐产物，再和亲电试剂反应，得到二取代的产物。具体技术方案如下：
金属氢化物/钯化合物体系在制备3,3-二取代氧化吲哚中的应用。
3,3-二取代氧化吲哚的制备方法，以烯基活泼亚甲基化合物为底物、金属氢化物为还原剂、钯化合物为催化剂，还原反应，得到还原产物；以还原产物与亲电试剂反应，得到3,3-二取代氧化吲哚。
上述技术方案中，还原产物与亲电试剂反应结束后，加入饱和氯化铵水溶液中止反应，然后经过萃取、旋干、柱层析纯化得到还原产物。
本发明中，烯基活泼亚甲基化合物的化学结构式如下：
Figure 840263dest_path_image001
其中，R 1、R 2独立的选自氢、烷基、苯基、取代苯基、萘基、吡啶基、喹啉基。
烯基活泼亚甲基化合物的化学结构式中，烷基可以为甲基，取代苯基可以为卤素取代苯基、甲氧基取代苯基。
本发明中，所述金属氢化物包括氢化钠、氢化锂、氢化钾、氢化钙，优选氢化钠、氢化锂，更优选氢化钠；所述钯化合物包括为氯化钯、醋酸钯、Pd(MeCN) 2Cl 2、[(η 3-C 3H 5)PdCl] 2、Pd(TFA) 2、Pd(dppp)Cl 2、Pd 2(dba) 3、Pd(C 6H 5CN) 2Cl 2、Pd(OH) 2、Pd/C、Pd(PPh 3) 4、Pd(PPh 3) 2Cl 2，优选氯化钯、醋酸钯，更优选氯化钯。
本发明中，所述亲电试剂为溴化苄、碘甲烷、丙烯酸甲酯或者双氧水。
本发明中，所述钯化合物、金属氢化物、烯基活泼亚甲基化合物的摩尔比为(0.01～1) ∶(1～5) ∶1，优选为(0.03～0.1) ∶(1～3) ∶1，更优选为0.05∶(1.5～2.5) ∶1，最优选为0.05∶2∶1。
本发明中，反应在氮气气氛下、溶剂中进行；所述溶剂包括DMA(N,N-二甲基乙酰胺)、DMF、THF、DME或者二氧六环。
本发明中，还原反应的温度为-50℃～120℃，优选0～50℃，更优选室温；还原反应的时间为0.3～10小时，优选0.4～5小时，更优选0.5小时。还原产物与亲电试剂反应的环境、温度与还原反应一致。
 有益效果
本发明氢化钠/钯还原烯基活泼亚甲基化合物有以下几点优势：1）相比于硼氢化钠，氢化钠价格更加便宜（工业上硼氢化钠是以氢化钠为原料制备的）；相比于氢气/钯碳还原，氢化钠方法的安全性更高；2）氢化钠分子量小而且组成简单，反应中使用量少，所以用氢化钠做为还原剂是一种原子经济的方法；副产物除了无害的钠盐，没有其它废物产生；3）烯基活泼亚甲基化合物被氢化钠还原后的产物在后处理前是钠盐，这一点和现有的还原方法都不一样，具有反应活性的钠盐可以继续和亲电试剂反应，得到二取代的产物，拓展了烯基活泼亚甲基化合物的应用。并且在此一锅反应中，氢化钠的还原性和碱性都被充分利用，大大提高了反应的原子经济性和步骤经济性，降低了反应成本。
本发明的技术方案具体可以如下所述：氮气保护下，把钯化合物和金属氢化物悬浮于溶剂中搅拌，然后加入底物烯基活泼亚甲基化合物，在-50℃至120℃下反应0.3～10小时；再加入亲电试剂，继续反应直到原料反应完全，然后加入饱和氯化铵水溶液中止反应，用溶剂萃取，蒸干，柱层析纯化，得到产物。
烯基活泼亚甲基化合物的还原是有机合成中经常使用的化学反应，一般采用两类方法：一类是使用氢气/钯碳进行氢化还原，在这个过程中，氢气的使用是一个潜在的危险因素，操作不当就会引起着火、***；另一类是使用还原剂进行还原，价格较高且需要处理大量废水。本发明使用相对比较安全且价格低廉的金属氢化物代替氢气和还原剂用于烯基活泼亚甲基化合物的还原具有重要的意义；而且更重要的是，此方法充分发挥了氢化钠的还原性和碱性，可以进行一锅反应。
本发明的还原体系是还原烯基活泼亚甲基化合物的简易方法，所用的氢化物和钯化合物催化剂都是实验室中容易获得的试剂，相比于常用的氢气氢化方法和还原剂还原方法，此方法更易操作，安全性更高，条件温和，反应收率高，而且可以一锅两步反应，具有很高的原子经济性和步骤经济性。。
 本发明的实施方式
实施例1
Figure 131567dest_path_image002
氮气保护下，氯化钯 (1.7 mg, 0.01 mmol, 5 mol%)和氢化钠 (60% in oil, 16 mg, 0.4 mmol, 2 equiv)悬浮于DMA (1.0 mL)，室温搅拌5分钟，加入化合物 1a (0.2 mmol)在 DMA (0.5 mL)的溶液，然后在室温反应30分钟，原料反应完全后，加入溴化苄（1.5eq.），继续搅拌反应。待原料反应完后，加饱和氯化铵水溶液淬灭反应，用乙酸乙酯萃取，收集有机相，旋干溶剂得到粗产物，柱层析，最终得到化合物 3a，收率98%。 1H NMR (400 MHz, CDCl 3): δ 7.38-7.27 (m, 4H), 7.13-7.04 (m, 7H), 7.02-6.94 (m, 5H), 6.64 (d, J = 7.3 Hz, 2H), 6.21 (d, J = 7.7 Hz, 1H), 3.47 (d, J = 12.9 Hz, 2H), 3.25 (d, J = 12.9 Hz, 2H). 13C NMR (151 MHz, CDCl 3): δ 177.80, 144.12, 136.08, 134.37, 130.26, 130.14, 129.49, 128.06, 127.85, 127.76, 126.81, 126.65, 124.42, 122.23, 108.88, 56.67, 43.83. LR-MS (ESI): m/z 390.3 [M+H]+。
实施例2
Figure 601862dest_path_image003
氮气保护下，氯化钯 (1.7 mg, 0.01 mmol, 5 mol%)和氢化钠 (60% in oil, 16 mg, 0.4 mmol, 2 equiv)悬浮于DMA (1.0 mL)，室温搅拌5分钟，加入化合物 1a (0.2 mmol)在 DMA (0.5 mL)的溶液，然后在室温反应30分钟，原料反应完全后，加入碘甲烷（2.5eq.），继续搅拌反应。待原料反应完后，加饱和氯化铵水溶液淬灭反应，用乙酸乙酯萃取，收集有机相，旋干溶剂得到粗产物，柱层析，最终得到化合物 3b，收率98%。 1H NMR (400 MHz, Chloroform- d): δ 7.41 (t, J = 7.5 Hz, 2H), 7.37-7.28 (m, 2H), 7.15-7.02 (m, 5H), 6.94 (d, J = 7.6 Hz, 2H), 6.86 (d, J = 7.1 Hz, 2H), 6.55-6.45 (m, 1H), 3.27 (d, J = 12.8 Hz, 1H), 3.09 (d, J = 12.8 Hz, 1H), 1.63 (s, 3H). 13C NMR (151 MHz, CDCl 3): δ 179.27, 143.52, 136.20, 134.51, 132.95, 129.99, 129.56, 128.04, 127.85, 127.73, 126.77, 126.70, 123.47, 122.70, 109.15, 50.41, 45.56, 23.10. LR-MS (ESI): m/z 314.2 [M+H]+。
实施例3
Figure 66342dest_path_image004
氮气保护下，氯化钯 (1.7 mg, 0.01 mmol, 5 mol%)和氢化钠 (60% in oil, 16 mg, 0.4 mmol, 2 equiv)悬浮于DMA (1.0 mL)，室温搅拌5分钟，加入化合物 1a (0.2 mmol)在 DMA (0.5 mL)的溶液，然后在室温反应30分钟，原料反应完全后，加入丙烯酸甲酯（6 eq.），继续搅拌反应。待原料反应完后，加饱和氯化铵水溶液淬灭反应，用乙酸乙酯萃取，收集有机相，旋干溶剂得到粗产物，柱层析，最终得到化合物 3c，收率97%。 1H NMR (400 MHz, CDCl 3): δ 7.45-7.28 (m, 4H), 7.15-7.01 (m, 5H), 6.91 (d, J = 7.4 Hz, 2H), 6.84 (d, J = 7.1 Hz, 2H), 6.51-6.42 (m, 1H), 3.56 (s, 3H), 3.29 (d, J = 12.8 Hz, 1H), 3.11 (d, J = 12.7 Hz, 1H), 2.59-2.48 (m, 1H), 2.45-2.34 (m, 1H), 2.32-2.20 (m, 1H), 2.11-1.98 (m, 1H). 13C NMR (151 MHz, CDCl 3): δ 177.80, 173.27, 144.23, 135.51, 134.29, 130.04, 129.84, 129.60, 128.26, 128.19, 127.72, 126.76, 126.74, 123.83, 122.86, 109.24, 54.40, 51.77, 44.92, 32.04, 29.73. LR-MS (ESI): m/z 386.2 [M+H]+。
实施例4
Figure 938483dest_path_image005
氮气保护下，氯化钯 (1.7 mg, 0.01 mmol, 5 mol%)和氢化钠 (60% in oil, 16 mg, 0.4 mmol, 2 equiv)悬浮于DMA (1.0 mL)，室温搅拌5分钟，加入化合物 1a (0.2 mmol)在 DMA (0.5 mL)的溶液，然后在室温反应30分钟，原料反应完全后，加入双氧水（3 eq.），继续搅拌反应。待原料反应完后，加饱和氯化铵水溶液淬灭反应，用乙酸乙酯萃取，收集有机相，旋干溶剂得到粗产物，柱层析，最终得到化合物 3d，收率93%。 1H NMR (400 MHz, CDCl 3): δ 7.46-7.38 (m, 3H), 7.38-7.32 (m, 1H), 7.21-7.08 (m, 5H), 6.97 (d, J = 7.5 Hz, 2H), 6.92 (d, J = 7.2 Hz, 2H), 6.51 (d, J = 7.5 Hz, 1H), 3.45 (br, 1H), 3.37 (q, J = 12.5 Hz, 2H). 13C NMR (151 MHz, CDCl 3): δ 177.21, 143.56, 133.92, 133.82, 130.35, 129.73, 129.68, 129.04, 128.36, 127.99, 127.09, 126.55, 124.61, 123.46, 109.55, 78.09, 45.99. LR-MS (ESI): m/z 316.1 [M+H]+。

Claims (10)

  1. 金属氢化物/钯化合物体系在制备3,3-二取代氧化吲哚中的应用。
  2. 根据权利要求1所述的应用，其特征在于，所述金属氢化物包括氢化钠、氢化锂、氢化钾、氢化钙；所述钯化合物包括为氯化钯、醋酸钯、Pd(MeCN) 2Cl 2、[(η 3-C 3H 5)PdCl] 2、Pd(TFA) 2、Pd(dppp)Cl 2、Pd 2(dba) 3、Pd(C 6H 5CN) 2Cl 2、Pd(OH) 2、Pd/C、Pd(PPh 3) 4、Pd(PPh 3) 2Cl 2。
  3. 根据权利要求1所述的应用，其特征在于，制备3,3-二取代氧化吲哚时，以烯基活泼亚甲基化合物、亲电试剂为原料；所述烯基活泼亚甲基化合物的化学结构式如下：
    Figure 96990dest_path_image001
    其中，R 1、R 2独立的选自氢、烷基、苯基、取代苯基、萘基、吡啶基、喹啉基；所述亲电试剂为溴化苄、碘甲烷、丙烯酸甲酯或者双氧水。
  4. 根据权利要求1所述的应用，其特征在于，所述钯化合物、金属氢化物、烯基活泼亚甲基化合物的摩尔比为(0.01～1) ∶(1～5) ∶1。
  5. 3,3-二取代氧化吲哚的制备方法，以烯基活泼亚甲基化合物为底物、金属氢化物为还原剂、钯化合物为催化剂，还原反应，得到还原产物；以还原产物与亲电试剂反应，得到3,3-二取代氧化吲哚。
  6. 根据权利要求5所述的方法，其特征在于，还原产物与亲电试剂反应结束后，加入饱和氯化铵水溶液中止反应，然后经过萃取、旋干、柱层析纯化得到还原产物。
  7. 根据权利要求5所述的方法，其特征在于，烯基活泼亚甲基化合物的化学结构式如下：
    Figure 695462dest_path_image002
    其中，R 1、R 2独立的选自氢、烷基、苯基、取代苯基、萘基、吡啶基、喹啉基；
    所述金属氢化物包括氢化钠、氢化锂、氢化钾、氢化钙；
    所述钯化合物包括为氯化钯、醋酸钯、Pd(MeCN) 2Cl 2、[(η 3-C 3H 5)PdCl] 2、Pd(TFA) 2、Pd(dppp)Cl 2、Pd 2(dba) 3、Pd(C 6H 5CN) 2Cl 2、Pd(OH) 2、Pd/C、Pd(PPh 3) 4、Pd(PPh 3) 2Cl 2；所述亲电试剂为溴化苄、碘甲烷、丙烯酸甲酯或者双氧水。
  8. 根据权利要求5所述的方法，其特征在于，所述钯化合物、金属氢化物、烯基活泼亚甲基化合物的摩尔比为(0.01～1) ∶(1～5) ∶1。
  9. 根据权利要求5所述的方法，其特征在于，还原反应在氮气气氛下、溶剂中进行；还原反应的温度为-50℃～120℃，时间为0.3～10小时。
  10. 根据权利要求5所述的方法制备的3,3-二取代氧化吲哚。
PCT/CN2018/105579 2018-09-13 2018-09-13 3,3-二取代氧化吲哚及其制备方法 WO2020051853A1 (zh)

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