Lithium Hydroxide → HCID 51356122, compound

HRID 909068Notes

Reaction equation

HRID 909068 reaction equation
C[O:2][C:3](=[O:41])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11]([N:13]1[CH2:17][C@@H:16]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C@@:15]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=2[F:32])([C:23]#[N:24])[C@H:14]1[C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:34]=1[F:40])=[O:12].[Li+].[OH-]>C1COCC1.O>[Cl:39][C:35]1[C:34]([F:40])=[C:33]([C@@H:14]2[C@:15]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=3[F:32])([C:23]#[N:24])[C@H:16]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:17][N:13]2[C:11]([NH:10][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([OH:41])=[O:2])=[O:12])[CH:38]=[CH:37][CH:36]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 51356120HCID 51356120, compound

Product 1

HCID 51356122HCID 51356122, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of rac-2-{[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]amino}-benzoic acid methyl ester (53.0 mg, 0.0883 mmol, Example C3) in THF (3 mL) was added a solution of LiOH (Aldrich, 21.8 mg, 0.52 mmol) in water (2 mL) and the reaction mixture was stirred at rt for 23 hrs. The reaction mixture was partly concentrated and quenched with 1 N HCl (pH 4-5), extracted with EtOAc, and washed with water, saturated NaCl. The organic phase was separated, and dried over Na2SO4. The mixture was then concentrated to give 2-{[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-benzoic acid (49.1 mg, 95%). HRMS (ES+) m/z Calcd for C30H27Cl2F2N3O3+H [(M+H)+]: 586.1471; Found: 586.1474.

Workup

  1. concentrationThe reaction mixture was partly concentrated
  2. customquenched with 1 N HCl (pH 4-5)
  3. extractionextracted with EtOAc
  4. washwashed with water, saturated NaCl
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. concentrationThe mixture was then concentrated

Sources & evidence

ORD record
ord-07a1f3fe05d24f08ba96f2f4006ff52b
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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