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

HRID 1806942Notes

Reaction equation

HRID 1806942 reaction equation
[C:1]([O:5][C:6](=[O:18])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([CH2:16][CH3:17])([CH2:14][CH3:15])[CH2:12][CH3:13])([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[C:21]([F:38])=[C:22](/[CH:26]=[C:27](/[C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=2[F:37])\[C:28]#[N:29])[CH:23]=[CH:24][CH:25]=1.C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1>ClCCl.C(O)(C)(C)C>[C:1]([O:5][C:6]([CH:7]1[CH:26]([C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([Cl:19])[C:21]=2[F:38])[C:27]([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=2[F:37])([C:28]#[N:29])[CH:9]([CH2:10][C:11]([CH2:12][CH3:13])([CH2:16][CH3:17])[CH2:14][CH3:15])[NH:8]1)=[O:18])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59249629(Z)-3-(3-Chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrileHCID 178443501HCID 178443501, compound

Product 1

HCID 67297020rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-diethyl-butyl)-pyrrolidine-2-carboxylic acid tert-butyl esterYield 57%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

In a manner similar to the method described in Example 100b, [3,3-diethyl-pent-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 106a (1.8 g, 7 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (1.74 g, 5.6 mmol) prepared in Example 52a, AgF (1.1 g, 8.6 mmol), and triethylamine (1.95 mL, 14 mmol) in dichloromethane (150 mL) at room temperature for 18 h, followed by the reaction with DBU (7 ml) in tert-butanol (30 mL) at 100° C. for 2 h to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-diethyl-butyl)-pyrrolidine-2-carboxylic acid tert-butyl ester as a white gum (1.8 g, 57%).

Sources & evidence

ORD record
ord-860a74cc1b144f15b081ae3a2a7479ba
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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