N-but-2-enyl-2,2,2-trifluoro-N-(2-iodo-4-trifluoromethyl-phenyl)-acetamide → 3-ethyl-5-trifluoromethyl-1H-indole
Reaction equation
[CH2:1]([N:5]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=1I)C(=O)C(F)(F)F)[CH:2]=[CH:3][CH3:4]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:3]([C:2]1[C:13]2[C:12](=[CH:17][CH:16]=[C:15]([C:18]([F:19])([F:20])[F:21])[CH:14]=2)[NH:5][CH:1]=1)[CH3:4]Participants
6
Reactant 1
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 100 °C
Procedure
A solution of N-but-2-enyl-2,2,2-trifluoro-N-(2-iodo-4-trifluoromethyl-phenyl)-acetamide (12.7 g, 29 mmol) in DMF (60 mL) is treated with n-Bu4NCl (8.8 g, 32 mmol), Pd(OAc)2 (131 mg, 0.58 mmol), and stirred at 100° C. for 2 h. The mixture is cooled to rt, diluted with EtOAc (150 mL), filtered through a pad of silica gel, and washed with 1 M HCl (150 mL). The organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-30% EtOAc in heptane to afford 3-ethyl-5-trifluoromethyl-1H-indole (2.6 g, 42%). MS: 214 (M+H); 1H NMR (300 MHz, CDCl3): δ 8.08 (s, NH, 1H), 7.89 (s, 1H), 7.41 (m, 2H), 7.07 (m, 1H), 2.81 (q, 2H), 1.34 (t, 3H).
Workup
- temperatureThe mixture is cooled to rt
- filtrationfiltered through a pad of silica gel
- washwashed with 1 M HCl (150 mL)
- customThe organic layer is separated
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue is purified by silica gel chromatography
- washeluting with 10%-30% EtOAc in heptane
Sources & evidence
- ORD record
- ord-331f5ec9eee041d3a0ae83a86f134796
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258130B2
Reaction notes
Loading…