Hydrochloric Acid → Rac-4-{[(2r,3r,4r,5s)-3-(3-bromo-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid

HRID 1807232Notes

Reaction equation

HRID 1807232 reaction equation
C[O:2][C:3](=[O:40])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Br:24])[CH:19]=3)[C@:16]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[C@H:15]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:14]2)=[O:12])=[CH:6][CH:5]=1.[OH-].[Na+].CO.Cl>O1CCCC1>[Br:24][C:20]1[CH:19]=[C:18]([C@@H:17]2[C@:16]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[C@H:15]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:14][C@H:13]2[C:11]([NH:10][C:7]2[CH:6]=[CH:5][C:4]([C:3]([OH:40])=[O:2])=[CH:9][CH:8]=2)=[O:12])[CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 59249281Rac-4-{[(2r,3r,4r,5s)-3-(3-bromo-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl ester

Product 1

HCID 59249391Rac-4-{[(2r,3r,4r,5s)-3-(3-bromo-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acidYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of rac-4-{[(2R,3R,4R,5S)-3-(3-bromo-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl ester prepared in Example 340 (0.15 g, 0.25 mmol) in tetrahydrofuran (9 mL) was added an aqueous solution (1 N) of NaOH (9 mL, 9 mmol) and methanol (3 mL). The reaction mixture was heated at 80° C. for 2 h, and the “pH” of the solution was adjusted to 5 by aqueous HCl solution. The mixture was extracted ethyl acetate twice. The combined organic extracts were washed with water, brine, dried over MgSO4, and concentrated to give rac-4-{[(2R,3R,4R,5S)-3-(3-bromo-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid as a white solid (90 mg, 60%).

Workup

  1. extractionThe mixture was extracted ethyl acetate twice
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-14851d9f6e97460c813450382345bb1e
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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