Triethylamine → rac-(2R,3S,4R,5S)-5-[2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1807039Notes

Reaction equation

HRID 1807039 reaction equation
[C:1]([O:5][C:6](=[O:27])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([C:14]1[CH2:15][CH2:16][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:18][CH:19]=1)([CH3:13])[CH3:12])([CH3:4])([CH3:3])[CH3:2].[Cl:28][C:29]1[C:30]([F:47])=[C:31](/[CH:35]=[C:36](/[C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:40]=2[F:46])\[C:37]#[N:38])[CH:32]=[CH:33][CH:34]=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:35]([C:31]2[CH:32]=[CH:33][CH:34]=[C:29]([Cl:28])[C:30]=2[F:47])[C:36]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:40]=2[F:46])([C:37]#[N:38])[CH:9]([CH2:10][C:11]([C:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:16][CH:15]=2)([CH3:13])[CH3:12])[NH:8]1)=[O:27])([CH3:2])([CH3:3])[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 178451252HCID 178451252, compound

Product 1

HCID 67299523rac-(2R,3S,4R,5S)-5-[2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

In a manner similar to the method described in Example 100b, [3-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-3-methyl-but-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 127a (2.4 g, 6.4 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (1.8 g, 6.4 mmol) prepared in Example 52a, AgF (1.3 g, 10 mmol), and triethylamine (2 mL, 14.5 mmol) in dichloromethane (100 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)-5-[2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester as a light yellow solid (3.2 g, 81%).

Sources & evidence

ORD record
ord-27816a28da2d430aa790388110f5f17b
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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