Hydrochloric Acid → rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]amino}-benzoic acid

HRID 909060Notes

Reaction equation

HRID 909060 reaction equation
C([O:3][C:4](=[O:42])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([N:14]2[CH2:18][C@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=3[F:26])[C@:16]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])([C:27]#[N:28])[C@@H:15]2[CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:13])=[CH:7][CH:6]=1)C.[OH-].[Na+].Cl>CO>[Cl:25][C:21]1[C:20]([F:26])=[C:19]([C@H:17]2[CH2:18][N:14]([C:12]([NH:11][C:8]3[CH:7]=[CH:6][C:5]([C:4]([OH:42])=[O:3])=[CH:10][CH:9]=3)=[O:13])[C@@H:15]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C@@:16]2([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[F:36])[C:27]#[N:28])[CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 51355586rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-benzoic acid ethyl ester

Product 1

HCID 51355587rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]amino}-benzoic acidYield 53.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-benzoic acid ethyl ester (0.2 g, 0.32 mmol) in methanol (5 mL) was added an aqueous solution (1 N) of NaOH (5 mL, 5 mmol). The reaction mixture was stirred at room temperature for 20 h. The “pH” of the mixture was adjusted to 5-6 by diluted aqueous HCl solution. The mixture was partitioned between EtOAc and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (75% EtOAc in hexanes) to give rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]amino}-benzoic acid as a white solid (0.1 g, 50%). HRMS (ES+) m/z Calcd for C30H27Cl2F2N3O3+H [(M+H): 586.1471; Found: 586.1473.

Workup

  1. customThe mixture was partitioned between EtOAc and water
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (75% EtOAc in hexanes)

Sources & evidence

ORD record
ord-478b1dbf1bf04d05b2222a6fed7839eb
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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