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

HRID 585161Notes

Reaction equation

HRID 585161 reaction equation
I[CH2:2][O:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([F:18])([F:17])[F:16])[CH:13]=2)[C:8]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=2[O:27][CH3:28])([F:19])[C:7]1=[O:29])=[O:5].[C:30]([O:34][P:35]([O-:42])([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])([CH3:33])([CH3:32])[CH3:31].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:30]([O:34][P:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])([O:42][CH2:2][O:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([F:18])([F:17])[F:16])[CH:13]=2)[C@@:8]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=2[O:27][CH3:28])([F:19])[C:7]1=[O:29])=[O:5])=[O:36])([CH3:33])([CH3:32])[CH3:31]

Participants

4

Reactant 2

HCID 208227933-(5-Chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid iodomethyl esterHCID 22339116Tetra-n-butylammonium di-tert-butylphosphate

Product 1

HCID 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 esterYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 25 mL flask containing 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid iodomethyl ester ((S)-XIV) (0.200 g, 0.368 mmol) was added 5 mL anhydrous tetrahydrofuran, and tetrabutylammonium di-t-butylphosphate (0.199 g, 0.441 mmol). The reaction was heated to reflux and allowed to stir for 1 hour. The reaction was then cooled to room temperature, and the solvent was evaporated in vacuo. The crude foam was purified by flash chromatography (silica gel 4:1 Hexanes: EtOAc) producing the title compound (0.110 g, 48%) as a clear colorless oil. 1H NMR (CDCl3 400 MHz): δ=8.35 (s, 1H), 7.78 (s, 1H), 7.48 (d, 1H, J=7 Hz), 7.34 (d, 1H, J=7 Hz), 7.30 (d, 1H, J=7 Hz), 6.76 (d, 1H, J=7 Hz), 5.90 (d, 1H, J=12.4 Hz), 3.53 (s, 3H), 1.50 (s, 18H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux
  3. customthe solvent was evaporated in vacuo
  4. customThe crude foam was purified by flash chromatography (silica gel 4:1 Hexanes: EtOAc)

Sources & evidence

ORD record
ord-616636f64f18415b83ce5f434fa6e43f
Source dataset
uspto-grants-2005_08
Patent number
US06930100B2

Reaction notes

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