Triethylamine → rac-(2R,3S,4R,5S)-3-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-chloro-phenyl}-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1806875Notes

Reaction equation

HRID 1806875 reaction equation
[C:1]([O:5][C:6](=[O:15])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:4])([CH3:3])[CH3:2].[C:16]([Si:20]([CH3:45])([CH3:44])[O:21][CH2:22][CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=1/[CH:32]=[C:33](/[C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=1[F:43])\[C:34]#[N:35])([CH3:19])([CH3:18])[CH3:17].C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([CH:7]1[CH:32]([C:26]2[CH:27]=[C:28]([Cl:31])[CH:29]=[CH:30][C:25]=2[O:24][CH2:23][CH2:22][O:21][Si:20]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:45])[CH3:44])[C:33]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=2[F:43])([C:34]#[N:35])[CH:9]([CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])[NH:8]1)=[O:15])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 59249244(Z)-3-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-chloro-phenyl}-2-(4-chloro-2-fluoro-phenyl)-acrylonitrileHCID 178444818HCID 178444818, compound

Product 1

HCID 67296914rac-(2R,3S,4R,5S)-3-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-chloro-phenyl}-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl esterYield 18.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 1c, [3-methyl-but-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 1a (2.1 g, 10 mmol) was reacted with (Z)-3-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-chloro-phenyl}-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (3.7 g, 8 mmol) prepared in Example 84a, AgF (1.0 g, 8 mmol), and triethylamine (2.8 mL, 20 mmol) in dichloromethane (120 mL) at room temperature for 18 h to give rac-(2R,3S,4R,5S)-3-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-chloro-phenyl}-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester as a white foam (1.0 g, 18%).

Sources & evidence

ORD record
ord-fec33eddceb34f13a1272f3fdf6604cf
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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