Trifluoroacetic acid → (4-{[(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}-3-methoxy-phenyl)-acetic acid

HRID 417318Notes

Reaction equation

HRID 417318 reaction equation
C([O:5][C:6](=[O:47])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([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:10]([O:45][CH3:46])[CH:9]=1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[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:11]4[CH:12]=[CH:13][C:8]([CH2:7][C:6]([OH:47])=[O:5])=[CH:9][C:10]=4[O:45][CH3:46])=[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

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 53237984(4-{[(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}-3-methoxy-phenyl)-acetic acid tert-butyl ester

Product 1

HCID 58286331(4-{[(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}-3-methoxy-phenyl)-acetic acidYield 96.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of chiral (4-{[(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}-3-methoxy-phenyl)-acetic acid tert-butyl ester (0.16 g, 0.23 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (0.5 g). The reaction mixture was stirred at room temperature for 20 h, then concentrated. The “pH” of the residue was adjusted to 7 by aqueous saturated NaHCO3 solution. The mixture was extracted with ethyl acetate three times. The combined organic extract was washed with brine, dried over MgSO4, and concentrated, dried in vacuo to give chiral (4-{[(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}-3-methoxy-phenyl)-acetic acid as a light yellow solid (0.14 g, 95%).

Workup

  1. concentrationconcentrated
  2. extractionThe mixture was extracted with ethyl acetate three times
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customdried in vacuo

Sources & evidence

ORD record
ord-2447892944f1450096c18d074697da6c
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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