(Trifluoromethyl)trimethylsilane → (+/-)-tert-Butyl 5-methoxy-7-methyl-4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-indole-1-carboxylate

HRID 2173952Notes

Reaction equation

HRID 2173952 reaction equation
[CH:1]([C:3]1[C:11]([O:12][CH3:13])=[CH:10][C:9]([CH3:14])=[C:8]2[C:4]=1[CH:5]=[CH:6][N:7]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:2].C[Si](C)(C)[C:24]([F:27])([F:26])[F:25].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.[NH4+].[Cl-].[Cl-].[Na+].O>[CH3:13][O:12][C:11]1[C:3]([CH:1]([OH:2])[C:24]([F:27])([F:26])[F:25])=[C:4]2[C:8](=[C:9]([CH3:14])[CH:10]=1)[N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:6]=[CH:5]2

Participants

7

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 72191522tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701515(+/-)-tert-Butyl 5-methoxy-7-methyl-4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-indole-1-carboxylate

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (0.44 g, 1.52 mmol) in THF (7.24 mL), trimethyl(trifluoromethyl)silane (0.71 mL, 4.56 mmol) and then TBAF (1M in THF, 4.56 mL, 4.56 mmol) were added at 0° C., and the reaction was stirred at room temperature. After 20 minutes the reaction mixture was diluted with aq. NH4Cl and brine, extracted with EtOAc, and the organic extract was dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-70% EtOAc in heptanes) to provide the title compound. MS (ESI+) m/z 360.1 (M+H).

Workup

  1. extractionextracted with EtOAc
  2. extractionthe organic extract
  3. dry with materialwas dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by flash chromatography (0-70% EtOAc in heptanes)

Sources & evidence

ORD record
ord-ea5f183124e842c696fb0c1cbd6f2d95
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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