CN113999142B - Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine - Google Patents
Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine Download PDFInfo
- Publication number
- CN113999142B CN113999142B CN202111437236.8A CN202111437236A CN113999142B CN 113999142 B CN113999142 B CN 113999142B CN 202111437236 A CN202111437236 A CN 202111437236A CN 113999142 B CN113999142 B CN 113999142B
- Authority
- CN
- China
- Prior art keywords
- boc
- cyclohexanediamine
- trans
- heptane
- azabicyclo
- 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.)
- Active
Links
Classifications
-
- 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
- C07C269/06—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 by reactions not involving the formation of carbamate 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/26—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses a preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine, belonging to the technical field of organic synthesis. Reacting 7-azabicyclo [4.1.0] heptane as raw material with dicarbonyl di-tert-butyl ester under alkaline condition to generate N-Boc-7-azabicyclo [4.1.0] heptane 2; then the N-Boc-trans-1, 2-cyclohexanediamine 3 is obtained by ring opening with ammonia water at high temperature and high pressure; salifying and resolving (S) -3-cyclohexenecarboxylic acid, and dissociating to obtain N-Boc- (1S, 2S) -1, 2-cyclohexanediamine. The method has the advantages of simple reaction operation, relatively simple steps, recoverability of the resolving agent, and potential industrial amplification prospect.
Description
Technical Field
The invention relates to a preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine, belonging to the technical field of organic synthesis.
Background
The trans-1, 2-cyclohexanediamine has C2 symmetry, is used as chiral organic amine with a heterocyclic structure symmetry, is widely applied to the field of medicine, is an important medical intermediate, plays an important role in chemical linkage, and a chiral compound of the trans-1, 2-cyclohexanediamine can be combined with a biologically important molecule.
The N-Boc-trans-1, 2-cyclohexanediamine well solves the problem of reaction selection of one amino group. N-Boc-trans-1, 2-cyclohexanediamine is specifically classified into N-Boc-1S,2S-1, 2-cyclohexanediamine and N-Boc-1R,2R-1, 2-cyclohexanediamine. Wherein N-Boc- (1S, 2S) -1, 2-cyclohexanediamine can also be applied to synthesis of steric type antitumor platinum (II) complexes, and N-Boc-trans-1, 2-cyclohexanediamine can be coordinated with a transition metal center to form corresponding ligands.
Currently, the synthesis methods of such compounds are synthesized under alkaline conditions by searching the existing published patents and literature, and most of WO2019/180628A1, synlett,2017,28,1278, j.chem.soc., dalton trans.,2001,2188, eur.j.org.chem.,2018,2018,99 are synthesized by using a large excess of (1s,2s) -1,2-cyclohexanediamine/(1r,2r) -1,2-cyclohexanediamine and di-tert-butyl dicarbonate. The literature reports yields as high as 53.6-94% using this method, but the yields are calculated as molar equivalents of di-tert-butyl dicarbonate. This is clearly disadvantageous for the efficient reaction of the expensive starting materials (1R, 2R) -1, 2-cyclohexanediamine or (1S, 2S) -1, 2-cyclohexanediamine.
Therefore, it is necessary to deeply research the process of N-Boc-trans-1, 2-cyclohexanediamine, so as to avoid the reaction between di-tert-butyl dicarbonate and diamino, thereby avoiding the selectivity problem, and to provide a reaction route which has easily available raw materials, high reaction yield and stable production, so as to meet the increasing market demand.
Disclosure of Invention
In order to overcome the technical defects, the invention discloses a preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine. Reacting 7-azabicyclo [4.1.0] heptane as a raw material with dicarbonyl di-tert-butyl ester under an alkaline condition to generate N-Boc-7-azabicyclo [4.1.0] heptane 2; then the N-Boc-trans-1, 2-cyclohexanediamine 3 is obtained by ring opening with ammonia water at high temperature and high pressure; salifying and resolving (S) -3-cyclohexenecarboxylic acid, and dissociating to obtain N-Boc- (1S, 2S) -1, 2-cyclohexanediamine. The method has the advantages of simple reaction operation, relatively simple steps, recoverability of the resolving agent, and potential industrial amplification prospect.
The invention relates to a preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine, which comprises the following steps:
the first step is as follows: carrying out DMAP (dimethyl formamide) catalytic reaction on 7-azabicyclo [4.1.0] heptane and di-tert-butyl dicarbonate in a dichloromethane solvent to obtain N-Boc-7-azabicyclo [4.1.0] heptane 2;
the second step is that: mixing the intermediate 2 with ammonia water and a catalyst, and carrying out ring opening reaction at high temperature and high pressure to obtain N-Boc-trans-1, 2-cyclohexanediamine 3;
the third step: dissolving N-Boc-trans-1, 2-cyclohexanediamine 3 and (S) -3-cyclohexenecarboxylic acid in an organic solvent, heating to generate diastereoisomer salt, salifying, cooling, filtering, and adding alkali to dissociate to obtain N-Boc- (1S, 2S) -1, 2-cyclohexanediamine.
Further, in the first step, the molar ratio of 7-azabicyclo [4.1.0] heptane, di-tert-butyl dicarbonate and triethylamine is 1:1.0-1.5:1.2-1.5.
Furthermore, in the second step, the ammonia water is 25-28% ammonia water, the high temperature and high pressure are 95-100 ℃, and 0.6-1.0Mpa.
Further, in the second step, the catalyst is B (C) 6 H 5 ) 3 (ii) a The amount of catalyst added is 2-5wt% of compound 2.
Further, in the third step, the organic solvent is selected from 2-methyltetrahydrofuran, acetic acid/isopropanol mixed solvent; wherein the ethyl acetate/isopropanol ratio is 10:1 by volume.
Further, in the third step, the molar ratio of compound 3 to (S) -3-cyclohexenecarboxylic acid was 1:0.98 to 1.02.
Further, in the third step, mother liquor obtained by salt forming filtration is mainly N-Boc- (1R, 2R) -1, 2-cyclohexanediamine, and is concentrated, dissociated and further purified with (R) -3-cyclohexenecarboxylic acid salt forming dissociation.
Advantageous effects of the invention
1. By carrying out Boc protection on the source, the subsequent selectivity problem is avoided. The single chiral enantiomer is further separated by a crystallization resolution method. The resolving agent can be recycled. The mother liquid of crystallization can be recovered, and then the enantiomer of another chirality can be resolved.
2. The chiral purity of both N-Boc- (1S, 2S) -1, 2-cyclohexanediamine and N-Boc- (1R, 2R) -1, 2-cyclohexanediamine obtained by the present invention can reach more than 99.0% ee.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The invention is further illustrated by the following specific examples. These examples are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. After reading the description of the present invention, one skilled in the art can make various changes and modifications to the invention, and these equivalent changes and modifications also fall into the scope of the invention defined by the claims.
Example 1:
adding 7-azabicyclo [4.1.0] into a reaction bottle]Heptane (97.2 g,1.0 mol), DMAP2.2g, di-tert-butyl dicarbonate (261.9g, 1.2 mol) were dissolved in 600mL of dichloromethane. Controlling the temperature to be 0-5 ℃, dropwise adding triethylamine (126.5 g, 1.25mol), naturally heating to room temperature for reacting for 8 hours after dropwise adding, detecting by TLC to completely react, adjusting the pH value to be =7-8 by 1M hydrochloric acid, layering, extracting by 400mL of dichloromethane, combining organic phases, washing by 200mL of 20% potassium bisulfate aqueous solution, washing by saturated sodium carbonate aqueous solution, drying by anhydrous sodium sulfate, concentrating under reduced pressure, distilling under reduced pressure at 55-60 ℃ to obtain 7-azabicyclo [4.1.0]]182.1g of tert-butyl heptane-7-carboxylate, yield 92.2% and chemical purity 99.4%. 1 HNMR(400MHz,CDCl3):4.12-4.10(m,2H),1.74-1.46(m,4H),1.44(s,9H),1.21-1.10(m,4H).
Example 2:
adding 7-azabicyclo [4.1.0] into a high-pressure reaction kettle]98.7g (0.5 mol, 1eq) of tert-butyl heptane-7-carboxylate, 500mL of 25% aqueous ammonia, and 4.4g of triphenylboron were mixed and stirred uniformly. Heating to 95-100 deg.c and reaction at 0.8MPa for 5 hr. Cooling to room temperature, concentrating under reduced pressure to dryness, adding 400mL of dichloromethane and 200mL of 20% ammonium chloride solution for washing, extracting 200mL of aqueous phase dichloromethane, combining organic phases, drying the organic phases with anhydrous sodium sulfate, concentrating under reduced pressure, adding N-heptane, cooling to 10 ℃, separating out solids, and filtering to obtain 96.9g of N-Boc-trans-1, 2-cyclohexanediamine, wherein the yield is 90.4% and the chemical purity is 99.0%. 1 H NMR (400MHz, CDCl3): 4.51 (s, 1H), 3.12 (dt, J =4.0,10.8Hz, 1H), 2.33 (dt, J =4.0and J =10.8Hz, 1H), 1.84-2.02 (m, 2H), 1.68-1.72 (m, 2H), 1.51 (s, 2H), 1.44 (s, 9H), 1.02-1.33 (m, 4H). The catalyst was removed under the same conditions, and after 48 hours of reaction, 73% of the starting material remained.
Example 3:
adding N-Boc-trans-1, 2-cyclohexanediamine (85.7g, 0.4mol), (S) -3-cyclohexenecarboxylic acid (49.5g, 0.392mol) and 600mL of 2-methyltetrahydrofuran into a reaction bottle, uniformly mixing, heating to 70-75 ℃, reacting for 3-5 hours after reaction liquid is clear, cooling to 10-15 ℃ in a gradient (10 ℃/30 min), filtering, leaching filter cakes by using 2-methyltetrahydrofuran to obtain (S) -3-cyclohexenecarboxylic acid/N-Boc- (1S, 2S) -1, 2-cyclohexanediamine salt, and recovering the filtrate. Then putting the mixture into the kettle again, adding 300mL of dichloromethane, dropwise adding 20% sodium hydroxide aqueous solution to adjust the pH to be between 11 and 12, carrying out layering, extracting 150mL of aqueous dichloromethane for 3 times, combining organic phases, drying the organic phases by anhydrous sodium sulfate, concentrating the mixture under reduced pressure, adding N-heptane, cooling the mixture to 10 ℃, separating out solids, and filtering the solids to obtain 36.7g of N-Boc- (1S, 2S) -1, 2-cyclohexanediamine, wherein the yield is 85.6%, the GC content is 99.7%, and the ee content is 99.5%.
Example 4:
into a reaction flask were charged N-Boc-trans-1, 2-cyclohexanediamine (85.7g, 0.4mol), (S) -3-cyclohexenecarboxylic acid (49.5g, 0.392mol), 500mL of ethyl acetate and 50mL of isopropanol. Heating to reflux, reacting for 3-5 hours after the reaction solution is clear, reducing the temperature to 15-20 ℃ in a gradient manner (10 ℃/30 min), filtering, leaching a filter cake by using a mixed solution of ethyl acetate and isopropanol to obtain (S) -3-cyclohexenecarboxylic acid/N-Boc- (1S, 2S) -1, 2-cyclohexanediamine salt, and recovering the filtrate. Then the mixture was poured into a kettle again, 300mL of dichloromethane was added, 20% aqueous sodium hydroxide solution was added dropwise to adjust pH =11-12, the layers were separated, 150mL of aqueous dichloromethane was extracted for 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, N-heptane was added thereto, the temperature was reduced to 10 ℃ to precipitate a solid, and N-Boc- (1S, 2S) -1, 2-cyclohexanediamine was obtained by filtration at 31.2g, the molar yield was 72.7%, GC99.8%, and 98.4% ee.
Example 5
Adding the mother solution obtained in example 3 into a four-neck flask, dropwise adding a 20% sodium hydroxide aqueous solution to adjust the pH to be =11-12, layering, extracting dichloromethane with 150mL for 3 times (adding hydrochloric acid into an aqueous phase to adjust the pH to be =1.0-1.5, extracting with ethyl acetate, recovering S-3-cyclohexenecarboxylic acid), combining organic phases, drying with anhydrous sodium sulfate, concentrating under reduced pressure to be an immobile liquid, adding N-heptane, cooling to 10 ℃, separating out a solid, filtering and drying to obtain 45.1g of N-Boc-trans-1, 2-cyclohexanediamine, 77.2 ee (1R, 2R-configuration is main).
The filter cake was charged into the reaction flask again, and (R) -3-cyclohexenecarboxylic acid (25.2g, 0.2mol) and 315mL of 2-methyltetrahydrofuran were added. Heating to 70-75 ℃, reacting for 3-5 hours after the reaction solution is clear, reducing the temperature to 10-15 ℃ in a gradient manner (10 ℃/30 min), filtering, leaching a filter cake by using 2-methyltetrahydrofuran to obtain (R) -3-cyclohexenecarboxylic acid/N-Boc- (1R, 2R) -1, 2-cyclohexanediamine salt, and recovering the filtrate. And then putting the mixture into the kettle again, adding 300mL of dichloromethane, dropwise adding 20% sodium hydroxide aqueous solution to adjust the pH to be 11-12, carrying out layering, extracting 150mL of aqueous-phase dichloromethane for 3 times, combining organic phases, drying the organic phases by using anhydrous sodium sulfate, concentrating the mixture under reduced pressure, adding N-heptane, cooling the mixture to 10-15 ℃, separating out solids, and filtering the solids to obtain 36.4g of N-Boc- (1R, 2R) -1, 2-cyclohexanediamine. Yield 80.7%, GC99.7%,99.5% ee.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered as the technical solutions and the inventive concepts of the present invention within the technical scope of the present invention.
Claims (7)
1. A preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine is characterized by comprising the following steps:
the first step is as follows: carrying out DMAP (dimethyl formamide) catalytic reaction on 7-azabicyclo [4.1.0] heptane and di-tert-butyl dicarbonate in a dichloromethane solvent to obtain N-Boc-7-azabicyclo [4.1.0] heptane 2;
the second step: reacting N-Boc-7-azabicyclo [4.1.0]]Mixing heptane 2, ammonia water and a catalyst, and carrying out ring opening reaction at high temperature and high pressure to obtain N-Boc-trans-1, 2-cyclohexanediamine 3; the catalyst is B (C) 6 H 5 ) 3 (ii) a The high temperature and high pressure are 95-100 deg.C and 0.6-1.0Mpa;
the third step: dissolving N-Boc-trans-1, 2-cyclohexanediamine 3 and (S) -3-cyclohexenecarboxylic acid in an organic solvent, heating to generate diastereoisomer salt, salifying, cooling, filtering, and adding alkali to dissociate to obtain N-Boc- (1S, 2S) -1, 2-cyclohexanediamine.
2. The method of preparing chiral N-Boc-trans-1, 2-cyclohexanediamine of claim 1, wherein: in the first step, the molar ratio of 7-azabicyclo [4.1.0] heptane to di-tert-butyl dicarbonate is 1:1.0-1.5.
3. The method of preparing chiral N-Boc-trans-1, 2-cyclohexanediamine of claim 1, wherein: in the second step, the ammonia water is 25-28% ammonia water.
4. The method of preparing chiral N-Boc-trans-1, 2-cyclohexanediamine of claim 1, wherein: in the second step, the catalyst was added in an amount of 2-5wt% based on N-Boc-7-azabicyclo [4.1.0] heptane 2.
5. The method of preparing chiral N-Boc-trans-1, 2-cyclohexanediamine of claim 1, wherein: in the third step, the organic solvent is selected from 2-methyltetrahydrofuran, ethyl acetate/isopropanol mixed solvent; wherein the ethyl acetate/isopropanol ratio is 10:1 volume ratio.
6. The method of preparing chiral N-Boc-trans-1, 2-cyclohexanediamine of claim 1, wherein: in the third step, the molar ratio of N-Boc-trans-1, 2-cyclohexanediamine 3 to (S) -3-cyclohexenecarboxylic acid was 1:0.98 to 1.02.
7. The method of preparing chiral N-Boc-trans-1, 2-cyclohexanediamine of claim 1, wherein: in the third step, mother liquor obtained by salifying and filtering is mainly N-Boc- (1R, 2R) -1, 2-cyclohexanediamine, and the mother liquor is concentrated, dissociated and further purified with (R) -3-cyclohexenecarboxylic acid salifying and dissociating.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111437236.8A CN113999142B (en) | 2021-11-29 | 2021-11-29 | Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111437236.8A CN113999142B (en) | 2021-11-29 | 2021-11-29 | Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113999142A CN113999142A (en) | 2022-02-01 |
CN113999142B true CN113999142B (en) | 2023-01-24 |
Family
ID=79930839
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111437236.8A Active CN113999142B (en) | 2021-11-29 | 2021-11-29 | Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113999142B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115028553B (en) * | 2022-06-16 | 2024-03-26 | 上海瀚鸿科技股份有限公司 | Preparation method of chiral N-Boc/Cbz-cis- (1R, 2S) -cyclohexanediamine |
CN115819251B (en) * | 2022-12-20 | 2024-04-09 | 沧州普瑞东方科技有限公司 | Preparation method of (1R) -1- [3- (difluoromethyl) -2-fluorophenyl ] ethylamine |
CN116102465A (en) * | 2023-02-17 | 2023-05-12 | 珠海市海瑞德生物科技有限公司 | Process for producing optically active diamine compound |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101898970A (en) * | 2009-05-26 | 2010-12-01 | 东南大学 | N-monosubstituted trans-1,2-diaminocyclohexane derivatives and preparation method thereof |
CN102234295A (en) * | 2010-05-05 | 2011-11-09 | 东南大学 | Platinum (II) complex adopting N-alkyl substituted trans 1,2-diaminocyclohexane as ligand and preparation method thereof |
CN103787921A (en) * | 2014-01-14 | 2014-05-14 | 苏州国镝医药科技有限公司 | Method for preparing high-optical-purity trans-1,2-cyclodiamine |
CN106164047A (en) * | 2014-02-20 | 2016-11-23 | 武田药品工业株式会社 | 1,2 substituted cyclopentanes as orexin receptor antagonists |
CN113493398A (en) * | 2021-08-11 | 2021-10-12 | 中车长春轨道客车股份有限公司 | Preparation method of N-Boc-trans-cyclohexanediamine |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008039367A1 (en) * | 2006-09-22 | 2008-04-03 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Synthesis of trans-tert-butyl-2-aminocyclopentylcarbamate |
GB201318222D0 (en) * | 2013-10-15 | 2013-11-27 | Takeda Pharmaceutical | Novel compounds |
-
2021
- 2021-11-29 CN CN202111437236.8A patent/CN113999142B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101898970A (en) * | 2009-05-26 | 2010-12-01 | 东南大学 | N-monosubstituted trans-1,2-diaminocyclohexane derivatives and preparation method thereof |
CN102234295A (en) * | 2010-05-05 | 2011-11-09 | 东南大学 | Platinum (II) complex adopting N-alkyl substituted trans 1,2-diaminocyclohexane as ligand and preparation method thereof |
CN103787921A (en) * | 2014-01-14 | 2014-05-14 | 苏州国镝医药科技有限公司 | Method for preparing high-optical-purity trans-1,2-cyclodiamine |
CN106164047A (en) * | 2014-02-20 | 2016-11-23 | 武田药品工业株式会社 | 1,2 substituted cyclopentanes as orexin receptor antagonists |
CN113493398A (en) * | 2021-08-11 | 2021-10-12 | 中车长春轨道客车股份有限公司 | Preparation method of N-Boc-trans-cyclohexanediamine |
Also Published As
Publication number | Publication date |
---|---|
CN113999142A (en) | 2022-02-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113999142B (en) | Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine | |
CN112020498B (en) | Buvalracetam intermediate, preparation method thereof and preparation method of Buvalracetam | |
US7754889B2 (en) | Optically active transition metal-diamine compound and process for producing optically active alcohol with the same | |
CN114014787A (en) | Asymmetric synthesis method for preparing (2S,3R) -p-methylsulfonylphenylserine ethyl ester | |
WO2022050234A1 (en) | Method for producing formic acid salt, method for producing formic acid, catalyst for producing formic acid salt, and ruthenium complex | |
CN109096122B (en) | Process for preparing spermidine | |
CN114478273A (en) | Preparation method of metahydroxylamine bitartrate | |
CN113244951B (en) | Mesoporous molecular sieve supported catalyst and application thereof | |
CN108467353B (en) | Preparation method of enantiopure tert-butyl sulfinamide | |
CN114315609B (en) | Technological method for preparing cis-2-aminocyclohexanol | |
CN112645813B (en) | Preparation method of (R) -3-cyclohexene carboxylic acid | |
CN111170878B (en) | Method for preparing D-type or L-type tert-leucine | |
CN112174837B (en) | Method for synthesizing (R) -4-methoxy-alpha-methylphenethylamine | |
CN109705014B (en) | Novel chiral amine oxide ligand and preparation method thereof | |
CN113651772A (en) | Preparation method of cloperastine hydrochloride | |
CN108409615B (en) | Method for synthesizing enantiopure tert-butyl sulfenamide | |
CN109265385B (en) | Synthesis process of chiral catalyst | |
CN111454163A (en) | Synthesis method of 1-aminomethyl-1-cyclopropanol | |
CN115745912B (en) | Method for preparing high-purity ranolazine | |
CN114105848B (en) | Preparation method of cis-D-hydroxyproline derivative | |
CN117756622A (en) | Preparation method of key intermediate of sabatier | |
CN110835319B (en) | Synthesis method of benazepril intermediate and benazepril hydrochloride | |
CN114349711B (en) | Synthesis method of (R) -1-Boc-3-hydroxymethyl piperazine | |
CN114573473B (en) | Preparation method of (R) -alpha-aryl alanine ester derivative | |
CN115181047B (en) | Preparation method of chiral 3- (dimethylamino) pyrrolidine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |