Trifluoroacetic acid → rac-(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 (1-methyl-1H-pyrrol-2-yl)-amide

HRID 417353Notes

Reaction equation

HRID 417353 reaction equation
C(OC([C:8]1[N:9]([CH3:44])[C:10]([NH:13][C:14]([C@@H:16]2[NH:20][C@@H:19]([CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C@:18]3([C:33]4[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=4)[NH:27][C:26]3=[O:35])[C@H:17]2[C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:37]=2[F:43])=[O:15])=[CH:11][CH:12]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:44][N:9]1[CH:8]=[CH:12][CH:11]=[C:10]1[NH:13][C:14]([CH:16]1[NH:20][CH:19]([CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:18]2([C:33]3[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=3)[NH:27][C:26]2=[O:35])[CH:17]1[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:37]=1[F:43])=[O:15]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58286361HCID 58286361, compound

Product 1

HCID 76741112rac-(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 (1-methyl-1H-pyrrol-2-yl)-amideYield 109.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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}-1-methyl-1H-pyrrole-2-carboxylic acid tert-butyl ester (0.1 g, 0.16 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (2 mL). The reaction mixture was stirred at room temperature for 20 h, then concentrated. To the residue was added aqueous saturated NaHCO3 solution until “pH” became 7-8, and the mixture was extracted with ethyl acetate several times. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated to give rac-(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 (1-methyl-1H-pyrrol-2-yl)-amide as a light brown solid (95 mg, 93%).

Workup

  1. concentrationconcentrated
  2. additionTo the residue was added aqueous saturated NaHCO3 solution until “pH”
  3. extractionthe mixture was extracted with ethyl acetate several times
  4. extractionThe combined organic extract
  5. washwas washed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-404fa4246d45443685ebcc94d69d226c
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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