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Method for synthesizing (4S,5R)- half-ester

A synthetic method, cinchona technology, applied in the synthesis field of -half-ester, can solve the problems such as troublesome catalyst preparation, achieve high enantioselective catalytic effect, high chemical yield and optical purity, and low cost

Inactive Publication Date: 2008-04-09
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The yield and stereoselectivity of chiral half-esters prepared by this method are high, but there is a disadvantage that the preparation of the catalyst is troublesome.

Method used

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  • Method for synthesizing (4S,5R)- half-ester
  • Method for synthesizing (4S,5R)- half-ester
  • Method for synthesizing (4S,5R)- half-ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1 cis-1,3-dibenzylimidazolin-2-one-2H-furo[3,4-d]imidazole-2,4,6-trione (33.6g, 0.10mol), 9 -propargylquinine (32.4g, 0.10mol), carbon tetrachloride (600mL) and toluene (400mL) were placed in a dry reaction flask, and anhydrous methanol (40.5mL, 1.0mol) was added dropwise at -40°C, After the addition was complete, the reaction was stirred at -40°C for 60 hours. After the reaction was complete, the solvent was recovered under reduced pressure, cooled to room temperature, ethyl acetate (500 mL) was added to the residue and stirred for 15 min, then 2M hydrochloric acid (400 mL) was added and stirred at 10-15°C for 10 min, left to stand, and the organic layer was separated. water and sodium sulfate to dry. Filtration, the filtrate reclaims the solvent under reduced pressure, and the residue is recrystallized with benzene (150mL) to obtain a white crystalline powder I (R 1 =-H, Ar =-Ph, R 2 =-CH 3, 35g, 95%), mp149~150℃, [α] D 22 =+2.74° (c 0.20, CHCl 3 ). IR...

Embodiment 2

[0031] Example 2 cis-1,3-dibenzylimidazolin-2-one-2H-furo[3,4-d]imidazole-2,4,6-trione (33.6g, 0.10mol), 9 - propargyl quinine (32.4g, 0.10mol), carbon tetrachloride (600mL) and toluene (400mL) were placed in a dry reaction flask, and cyclohexanol (52.2mL, 0.50mol) was added dropwise at -40°C, After the addition was complete, the reaction was stirred at -40°C for 60 hours. After the reaction was complete, the solvent was recovered under reduced pressure, cooled to room temperature, ethyl acetate (500 mL) was added to the residue and stirred for 15 min, then 2M hydrochloric acid (400 mL) was added and stirred at 10-15 ° C for 15 min, and the organic layer was separated. water and sodium sulfate to dry. Filtration, the filtrate reclaims the solvent under reduced pressure, and the residue is recrystallized with benzene (160mL) to obtain a white crystalline powder I (R 1 -H, Ar = -Ph, R 2 =cyclohexyl, 37.4g, 87%), mp172~175°C, [α] D 22 =+2.70° (c 0.20, CHCl 3 ), [α] D 25 =...

Embodiment 3

[0032] Example 3 cis-1,3-dibenzylimidazolin-2-one-2H-furo[3,4-d]imidazole-2,4,6-trione (33.6g, 0.10mol), 9 - Propargyl dihydroquinine (32.6g, 0.10mol), carbon tetrachloride (600mL) and toluene (400mL) were placed in a dry reaction flask, and anhydrous methanol (40.5mL, 1.0mol ), the reaction was stirred at -40°C for 60 hours after addition. After the reaction was complete, the solvent was recovered under reduced pressure, cooled to room temperature, ethyl acetate (500 mL) was added to the residue and stirred for 15 min, then 2M hydrochloric acid (400 mL) was added and stirred at 10-15°C for 10 min, left to stand, and the organic layer was separated. water and sodium sulfate to dry. Filtration, the filtrate reclaims the solvent under reduced pressure, and the residue is recrystallized with toluene (200mL) to obtain a white crystalline powder I (R 1 -H, Ar = -Ph, R 2 =-CH 3 , 33.2g, 90%), mp148~150℃, [α] D 22 =+2.70° (c 0.20, CHCl 3 ).

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Abstract

The invention pertains to the technical field of organic chemistry, in particular to a synthesis method of (4S, 5R)-semi-ester. The method carries out the enantioselective open-loop of cyclic acid anhydride and alcohol under the catalysis of cinchona alkaloid so as to prepare the (4S, 5R)-semi-ester. The reaction is carried out in the organic solvent in the states of normal pressure, compression or decompression, the reaction temperature is -80 DEG C to 25 DEG C, the reaction time is 10 to 80 hours, the total yield is more than 90 percent, and the ee is more than 98.5 percent. The raw materials of the method of the invention are easy to obtain, the catalyst can be reclaimed quantitatively, the reaction conditions are mild, and the yield and the stereoselectivity are high, so the invention is applicable to industrialization production.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry, and specifically relates to a method for synthesizing (4S, 5R)-half esters as shown in formula I. [0002] [0003] where R 1 for hydrogen, C 1 ~C 6 Alkyl, phenyl, p-tolyl, p-methoxyphenyl, 3,4-dimethylphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethylphenyl, 3,4,5-trimethoxyphenyl, p-chlorophenyl, Ar is phenyl, p-tolyl, p-methoxyphenyl, 3,4-dimethylphenyl, 3,4-dimethoxy phenyl, 3,4,5-trimethylphenyl, 3,4,5-trimethoxyphenyl, p-chlorophenyl, thienyl, furyl or naphthyl; R 2 for C 1 ~C 6 Alkyl, C 3 ~C 6 Cycloalkyl, C 2 ~C 6 Alkenyl, aralkyl or aralkenyl. Background technique [0004] It is known that the (4S, 5R)-half ester represented by formula I is a key intermediate in the synthesis of d-biotin (d-Biotin, vitamin H, coenzyme R). [0005] The synthesis of (4S, 5R)-half ester was first reported by Gerecke et al. (Helv Chim Acta, 1970, 53, 991), and the monoesterification of cycl...

Claims

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Application Information

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IPC IPC(8): C07D233/34B01J31/02C07B53/00
CPCC07D233/32B01J31/0244C07D491/048C07D487/04B01J31/0237C07D453/02
Inventor 陈芬儿黄建戴惠芳熊非
Owner FUDAN UNIV
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