Water → (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'-carboxylic acid [4-(2-methanesulfonyl-ethoxy)-2-methoxy-phenyl]-amide

HRID 417329Notes

Reaction equation

HRID 417329 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][S:12][CH3:13])[CH:6]=[CH:5][C:4]=1[NH:14][C:15]([C@@H:17]1[NH:21][C@@H:20]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C@:19]2([C:34]3[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=3)[NH:28][C:27]2=[O:36])[C@H:18]1[C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[C:38]=1[F:44])=[O:16].ClC1C=C(C=CC=1)C(OO)=[O:50].[OH2:56]>ClCCl>[CH3:13][S:12]([CH2:11][CH2:10][O:9][C:7]1[CH:6]=[CH:5][C:4]([NH:14][C:15]([C@@H:17]2[NH:21][C@@H:20]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C@:19]3([C:34]4[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=4)[NH:28][C:27]3=[O:36])[C@H:18]2[C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[C:38]=2[F:44])=[O:16])=[C:3]([O:2][CH3:1])[CH:8]=1)(=[O:50])=[O:56]

Participants

5

Reactant 3

HCID 962WaterHCID 70297m-Chloroperbenzoic acidHCID 58286316(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'-carboxylic acid [2-methoxy-4-(2-methylsulfanyl-ethoxy)-phenyl]-amide

Product 1

HCID 58286304(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'-carboxylic acid [4-(2-methanesulfonyl-ethoxy)-2-methoxy-phenyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of chiral (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′-carboxylic acid [2-methoxy-4-(2-methylsulfanyl-ethoxy)-phenyl]-amide (0.17 g, 0.26 mmol) prepared in Example 169 in dichloromethane (5 mL) was added 3-chloroperoxybenzoic acid (MCPBA, Aldrich, 77%) (0.11 g mL, 0.52 mmol). The reaction mixture was stirred at room temperature for 2 h. The crude mixture was diluted with water, and extracted with dichloremethane three times. The combined organic extract was washed with aqueous saturated Na2S2O3 solution, brine, dried over MgSO4, and concentrated. TLC analysis indicated the complete consumption of starting material and the formation of two major products. The residue was purified by chromatography (0-50% EtOAc in dichlormethane) to give the first product chiral (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′-carboxylic acid [4-(2-methanesulfonyl-ethoxy)-2-methoxy-phenyl]-amide as a light red solid (Yield, 98 mg, 55%).

Workup

  1. extractionextracted with dichloremethane three times
  2. extractionThe combined organic extract
  3. washwas washed with aqueous saturated Na2S2O3 solution, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customthe complete consumption of starting material
  7. customThe residue was purified by chromatography (0-50% EtOAc in dichlormethane)
  8. customto give

Sources & evidence

ORD record
ord-c71d6b63bed043b1854701b9ba12a200
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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