Lithium Hydroxide → HCID 51356415, compound

HRID 909071Notes

Reaction equation

HRID 909071 reaction equation
C([O:3][C:4](=[O:39])[CH2:5][CH2:6][CH2:7][NH:8][C:9]([N:11]1[CH2:15][C@@H:14]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C@@:13]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[F:30])([C:21]#[N:22])[C@H:12]1[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[F:38])=[O:10])C.[Li+].[OH-]>C1COCC1.O>[Cl:37][C:33]1[C:32]([F:38])=[C:31]([C@@H:12]2[C@:13]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[F:30])([C:21]#[N:22])[C@H:14]([CH2:16][C:17]([CH3:19])([CH3:20])[CH3:18])[CH2:15][N:11]2[C:9]([NH:8][CH2:7][CH2:6][CH2:5][C:4]([OH:39])=[O:3])=[O:10])[CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 51356414HCID 51356414, compound

Product 1

HCID 51356415HCID 51356415, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture rac-4-{[(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}-butyric acid ethyl ester (98.6 mg, 0.170 mmol, Example C10) in THF (6 mL) was added a solution of LiOH (Aldrich, 47.1 mg, 1.12 mmol) in water (4 mL) and the reaction mixture was stirred at rt for 6 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 rac-4-{[(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}-butyric acid (93.9 mg, 100%). HRMS (ES+) m/z Calcd for C27H29Cl2F2N3O3+H [(M+H)+]: 552.1627; Found: 552.1628.

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-ed3af5473314465cb5777165102c96ff
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

Loading…