Dichloromethane → rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-cyclohexylmethyl-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1806797Notes

Reaction equation

[C:1]([O:5][C:6](=[O:17])[CH2:7]/[N:8]=[CH:9]/[CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].[Cl:18][C:19]1[C:20]([F:36])=[C:21](/[CH:25]=[C:26](/[C:29]2[CH:34]=[CH:33]C(Cl)=[CH:31][CH:30]=2)\[C:27]#[N:28])[CH:22]=[CH:23][CH:24]=1.C(N(CC)CC)C.Cl[CH2:45][Cl:46]>>[C:1]([O:5][C:6]([CH:7]1[CH:25]([C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([Cl:18])[C:20]=2[F:36])[C:26]([C:29]2[CH:30]=[CH:31][C:45]([Cl:46])=[CH:33][CH:34]=2)([C:27]#[N:28])[CH:9]([CH2:10][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]2)[NH:8]1)=[O:17])([CH3:4])([CH3:2])[CH3:3]

Participants

Reactant 4

HCID 6344Dichloromethane

HCID 8471Triethylamine

HCID 59249283(Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-phenyl)-acrylonitrile

HCID 178451247HCID 178451247, compound

Product 1

HCID 67296915rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-cyclohexylmethyl-pyrrolidine-2-carboxylic acid tert-butyl esterYield 55%

Procedure

In a manner similar to the method described in Example 1c, [2-cyclohexyl-eth-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 59a (2.3 g, 10 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-phenyl)-acrylonitrile (1.9 g, 6.5 mmol) prepared in Example 26a, AgF (1.7 g, 13 mmol), and triethylamine (2.6 g, 26 mmol) in dichloromethane (100 mL) at room temperature for 18 h to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-cyclohexylmethyl-pyrrolidine-2-carboxylic acid tert-butyl ester as a white foam (1.9 g, 55%).

Sources & evidence

ORD record: ord-ae75c684e7ca4722b9f4dfc3805faaf9
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354444B2

Reaction notes

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