Dimethylformamide → HCID 68555508, compound
Reaction equation
[H-].[Na+].[CH2:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][C:15]([F:18])([F:17])[F:16])[CH:12]=2)[NH:7][CH:6]=1)[CH3:4].C[N:20](C=O)C>>[CH2:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][C:15]([F:18])([F:16])[F:17])[CH:12]=2)[N:7]([NH2:20])[CH:6]=1)[CH3:4]Participants
Conditions
- Temperature
- 0 °C
Procedure
A suspension of NaH (7.9 g, 197 mmol, 60% in mineral oil) in DMF (60 mL) at 0° C. is treated with 3-ethyl-5-trifluoromethoxy-1H-indole (3 g, 13.1 mmol) and stirred at 0° C. for 1 h. The mixture is treated with HOSA (7.4 g, 65.5 mmol) portion wise and warmed to rt over 2 h. The mixture is then poured over ice and filtered through a pad of Celite. 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 10%-30% EtOAc in heptane to afford 3-ethyl-5-trifluoromethoxy-indol-1-ylamine (2.05 g, 64%). MS: 245 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.37 (m, 2H), 7.11 (m, 1H), 7.00 (s, 1H), 4.72 (s, NH2, 2H), 2.73 (q, 2H), 1.29 (t, 3H).
Workup
- additionThe mixture is treated with HOSA (7.4 g, 65.5 mmol) portion wise
- temperaturewarmed to rt over 2 h
- additionThe mixture is then poured over ice
- filtrationfiltered through a pad of Celite
- 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 10%-30% EtOAc in heptane
Sources & evidence
- ORD record
- ord-4354e1986aa34f0a8840c398acc39f52
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258130B2
Reaction notes
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