Lithium Hydroxide → HCID 51355301, compound

HRID 909050Notes

Reaction equation

HRID 909050 reaction equation
C[O:2][C:3](=[O:35])[CH2:4][C:5]([N:7]1[CH2:11][C@@H:10]([CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C@@:9]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[F:26])([C:17]#[N:18])[C@H:8]1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[C:28]=1[F:34])=[O:6].[Li+].[OH-]>C1COCC1.CO>[Cl:33][C:29]1[C:28]([F:34])=[C:27]([C@@H:8]2[C@:9]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=3[F:26])([C:17]#[N:18])[C@H:10]([CH2:12][C:13]([CH3:14])([CH3:15])[CH3:16])[CH2:11][N:7]2[C:5](=[O:6])[CH2:4][C:3]([OH:35])=[O:2])[CH:32]=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67095278HCID 67095278, compound

Product 1

HCID 51355301HCID 51355301, compound

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of methyl malonyl chloride (Aldrich, 127 mg, 0.93 mmol), DIPEA (Aldrich, 297.0 mg, 2.3 mmol) and rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (150 mg, 0.35 mmol) was stirred at rt overnight. The reaction mixture was concentrated and purified by RP-HPLC to give rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-3-oxo-propionic acid methyl ester (136.2 mg, 73.5%). In a manner similar to the method described in Example 8, rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-3-oxo-propionic acid methyl ester (120 mg, 0.23 mmol) was treated with 2 N LiOH (1.0 mL) in THF/MeOH (3 mL/1 mL) at rt for 3 hrs and purified by RP-HPLC to rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-3-oxo-propionic acid (21.2 mg, 18.2%). HRMS (ES+) m/z Calcd for C25H24Cl2F2N2O3+H [(M+H): 509.1205; Found: 509.1207.

Workup

  1. custompurified by RP-HPLC to rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-3-oxo-propionic acid (21.2 mg, 18.2%)

Sources & evidence

ORD record
ord-a3c1cb20770e48868f7cd27c3fc3e47a
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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