Lithium Hydroxide → HCID 51357533, compound

HRID 909095Notes

Reaction equation

HRID 909095 reaction equation
C([O:3][C:4](=[O:42])[CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([N:14]2[CH2:18][C@@H:17]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C@@:16]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])([C:24]#[N:25])[C@H:15]2[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=2[F:41])=[O:13])[CH2:8][CH2:7]1)C.[Li+].[OH-]>C1COCC1.O>[Cl:40][C:36]1[C:35]([F:41])=[C:34]([C@@H:15]2[C@:16]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])([C:24]#[N:25])[C@H:17]([CH2:19][C:20]([CH3:21])([CH3:22])[CH3:23])[CH2:18][N:14]2[C:12]([N:9]2[CH2:8][CH2:7][CH:6]([CH2:5][C:4]([OH:42])=[O:3])[CH2:11][CH2:10]2)=[O:13])[CH:39]=[CH:38][CH:37]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 51357532HCID 51357532, compound

Product 1

HCID 51357533HCID 51357533, compoundYield 93.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of rac-{1-[(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]-piperidin-4-yl}-acetic acid ethyl ester (33.0 mg, 0.053 mmol) in THF (3 mL) was added a solution of LiOH (Aldrich, 15.7 mg, 0.374 mmol) in water (1.5 mL) and the reaction mixture was stirred at rt for 24 hrs. The reaction mixture was partly concentrated and quenched with 1 N HCl (pH 6-7), 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-{1-[(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]-piperidin-4-yl}-acetic acid (29.5 mg, 93.6%). HRMS (ES+) m/z Calcd for C30H33Cl2F2N3O3+H [(M+H)+]: 592.1940; Found: 592.1940.

Workup

  1. concentrationThe reaction mixture was partly concentrated
  2. customquenched with 1 N HCl (pH 6-7)
  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-08e57934afdd4889b0c03bd07b2978c9
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

Loading…