Hydrochloric Acid → rac-5-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-benzo[b]thiophene-2-carboxylic acid

HRID 417370Notes

Reaction equation

HRID 417370 reaction equation
C[O:2][C:3]([C:5]1[S:9][C:8]2[CH:10]=[CH:11][C:12]([NH:14][C:15]([C@@H:17]3[NH:21][C@@H:20]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C@:19]4([C:34]5[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=5)[NH:28][C:27]4=[O:36])[C@H:18]3[C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[C:38]=3[F:44])=[O:16])=[CH:13][C:7]=2[CH:6]=1)=[O:4].Cl>C1COCC1.O.C(OCC)(=O)C>[Cl:35][C:31]1[CH:30]=[C:29]2[NH:28][C:27](=[O:36])[C@:19]3([C@@H:18]([C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[C:38]=4[F:44])[C@H:17]([C:15]([NH:14][C:12]4[CH:11]=[CH:10][C:8]5[S:9][C:5]([C:3]([OH:4])=[O:2])=[CH:6][C:7]=5[CH:13]=4)=[O:16])[NH:21][C@H:20]3[CH2:22][C:23]([CH3:25])([CH3:24])[CH3:26])[C:34]2=[CH:33][CH:32]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 66624521rac-5-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-benzo[b]thiophene-2-carboxylic acid methyl ester

Product 1

HCID 66624667rac-5-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-benzo[b]thiophene-2-carboxylic acidYield 100%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of rac-5-{[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]amino}-benzo[b]thiophene-2-carboxylic acid methyl ester (42 mg, 0.065 mmol) in THF (3 mL) was added LiOH monohydrate (11 mg, 0.26 mmol) in water (2 mL) and the reaction mixture was allowed to stir at rt overnight. The mixture was then treated with 1N HCl to slightly acidic, diluted with ethyl acetate (80 mL), washed with water (2×15 mL), dried with Na2SO4 and concentrated to give rac-5-{[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]amino}-benzo[b]thiophene-2-carboxylic acid as a white solid (41 mg, 100%). MS (ES+) m/z [(M+H)+]: 640

Workup

  1. washwashed with water (2×15 mL)
  2. dry with materialdried with Na2SO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-94732e864e5e4216a559da852e8afa0c
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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