Trifluoroacetic acid → (S)-3-(5-Chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid phosphonooxymethyl ester

HRID 585162Notes

Reaction equation

HRID 585162 reaction equation
C([O:5][P:6]([O:37]C(C)(C)C)([O:8][CH2:9][O:10][C:11]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]([F:25])([F:24])[F:23])[CH:20]=2)[C@@:15]([C:27]2[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=2[O:34][CH3:35])([F:26])[C:14]1=[O:36])=[O:12])=[O:7])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[P:6]([O:8][CH2:9][O:10][C:11]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]([F:23])([F:24])[F:25])[CH:20]=2)[C@@:15]([C:27]2[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=2[O:34][CH3:35])([F:26])[C:14]1=[O:36])=[O:12])([OH:7])([OH:37])=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69330817(S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid di-tert-butoxy-phosphoryloxymethyl ester

Product 1

HCID 10239334(S)-3-(5-Chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid phosphonooxymethyl esterYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 25 mL flask containing (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid di-tert-butoxy-phosphoryloxymethyl ester ((S)-XV) (0.110 g, 0.176 mmol) was added 2 mL anhydrous dichloromethane, and trifluoroacetic acid (0.060 g, 0.527 mmol). The reaction was allowed to stir at room temperature for 4 hours. The dichloromethane was evaporated in vacuo, and the crude foam was purified by reverse phase chromatography (C18 2:1CH3CN:H2O) producing the title compound (0.070 g, 78%) as a white powder. 1H NMR (CDCl3 400 MHz): δ=8.26 (s, 1H), 7.68 (s, 1H), 7.45 (d, 1H, J=7 Hz), 7.28-7.24 (m, 2H), 6.72 (d, 1H, J=7 Hz), 5.90-5.81 (m, 2H), 3.48 (s, 3H); 31P NMR (CDCl3 162 MHz) δ=−0.233; 19F NMR (CDCl3 376 MHz) δ=−63.3, −153.8; LRMS [M−H]−511.4, [M+NH4]+530.9.

Workup

  1. customThe dichloromethane was evaporated in vacuo
  2. customthe crude foam was purified by reverse phase chromatography (C18 2:1CH3CN:H2O)

Sources & evidence

ORD record
ord-4350699f4ce94524932825693ed3152c
Source dataset
uspto-grants-2005_08
Patent number
US06930100B2

Reaction notes

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