Lithium hydroxide, monohydrate → 4-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acid

HRID 1807266Notes

Reaction equation

HRID 1807266 reaction equation
C[O:2][C:3](=[O:43])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]([C@H:14]2[C@H:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=3[F:26])[C@:17]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])([C:27]#[N:28])[C@H:16]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:15]2)=[O:13])=[CH:6][C:5]=1[F:42].O.[OH-].[Li+]>C1COCC1.O>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([C@@:17]2([C:27]#[N:28])[C@H:16]([CH2:37][C:38]([CH3:40])([CH3:41])[CH3:39])[NH:15][C@@H:14]([C:12]([NH:11][CH2:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:43])=[O:2])=[C:5]([F:42])[CH:6]=3)=[O:13])[C@@H:18]2[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=2[F:26])=[C:30]([F:36])[CH:31]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 53357095Rac-4-({[(2r,3s,4r,5s)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acid methyl ester

Product 1

HCID 533570944-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acidYield 97.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a manner similar to the method described in Example 380, rac-4-({[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acid methyl ester (80.3 mg, 0.127 mmol) in THF (9 ml) was reacted with lithium hydroxide hydrate (37.6 mg, 0.896 mmol) in water (4.5 mL) to give rac-4-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acid as a white lyophilized solid (76.5 mg, 97%). HRMS (ES+) m/z Calcd C31H28Cl2F3N3O3+H [(M+H): 618.1533. Found: 618.1533.

Sources & evidence

ORD record
ord-dc02a547e67348b29173efc92ebac50a
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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