Water → 3-ethyl-5-(trifluoromethoxy)-1H-indole
Reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[N:13]([CH2:20][CH:21]=[CH:22][CH3:23])C(=O)C(F)(F)F.O>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:22]([C:21]1[C:2]2[C:3](=[CH:4][CH:5]=[C:6]([O:8][C:9]([F:10])([F:11])[F:12])[CH:7]=2)[NH:13][CH:20]=1)[CH3:23]Participants
6
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 100 °C
Procedure
A solution of N-(2-bromo-4-trifluoromethoxy-phenyl)-N-but-2-enyl-2,2,2-trifluoro-acetamide (10 g, 24.7 mmol) in DMF (50 mL) is treated with n-Bu4NCl (7.5 g, 27.2 mmol), Pd(OAc)2 (221 mg, 0.98 mmol), and stirred at 100° C. for 1 h. H2O (10 mL) is added, and the mixture is cooled to rt, filtered through a pad of silica gel. The filtrate is extracted with heptane (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0%-25% EtOAc in heptane to afford 3-ethyl-5-trifluoromethoxy-1H-indole (3.1 g, 55%). MS: 230 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.97 (s, NH, 1H), 7.44 (s, 1H), 7.29 (m, 1H), 7.07 (m, 2H), 2.77 (q, 2H), 1.32 (t, 3H).
Workup
- temperaturethe mixture is cooled to rt
- filtrationfiltered through a pad of silica gel
- extractionThe filtrate is extracted with heptane (3×50 mL)
- dry with materialThe combined organic layer is dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue is purified by silica gel chromatography
- washeluting with 0%-25% EtOAc in heptane
Sources & evidence
- ORD record
- ord-c961025cb4d64f949dd418d96174df80
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258130B2
Reaction notes
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