Hydrochloric Acid → 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoic acid

HRID 1807282Notes

Reaction equation

HRID 1807282 reaction equation
[Cl:1][C:2]1[C:3]([F:43])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C:39]([O:41]C)=[O:40])=[CH:33][CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.O.[OH-].[Li+].Cl>C1COCC1.O>[Cl:1][C:2]1[C:3]([F:43])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:32]=[CH:33][C:34]([CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[CH:35][CH:36]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 53357489methyl 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoate

Product 1

HCID 533574903-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoic acidYield 100.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of chiral methyl 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoate (58.8 mg, 0.0936 mmol) in THF (5 ml) was treated with LITHIUM HYDROXIDE MONOHYDRATE (15.7 mg, 0.374 mmol) in water (2.5 ml) and stirred at rt overnight. The mixture was then treated with 1 N HCl to pH 3-4, extracted with ethyl acetate. The organic extracts were washed with water and brine, dried over sodium sulfate and concentrated to give chiral 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoic acid (57.7 mg, 100%) as a white solid. MS (ES+) m/z Calcd: [(M+H)+]: 614.17. found: 614.2.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic extracts were washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-c21120a4ba6643c5856866fa1aae637c
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

Loading…