Dimethylformamide → 5-(Trifluoromethyl)-1h-indole-3-carbaldehyde
Reaction equation
P(Cl)(Cl)(Cl)=O.[F:6][C:7]([F:18])([F:17])[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[CH:11]2.[OH-].[Na+].CN([CH:24]=[O:25])C>>[F:18][C:7]([F:6])([F:17])[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH:24]=[O:25]Participants
Procedure
Phosphorous oxychloride (7.6 mL, 83.0 mmol) was added dropwise to DMF (150 mL) at 0° C. A solution of 5 (4.5 g, 24.4 mmol) in DMF (30 mL) was added after 15 min. and the reaction mixture was allowed to warm to room temperature for 2 h. The mixture was poured on ice-water (300 g), made alkaline (pH 7-8) with 2 N aq. NaOH, extracted with EtOAc, the extracts were washed with brine, dried (MgSO4), and concentrated. The crude product was purified by flash chromatography on silica gel using 10% MeOH/CHCl3 as eluent. Recrystallization by dissolving yellow solid in hot MeOH and pouring onto cold water afforded 1 (3.9 g, 75% yield) as a white solid. Mp 242-243° C. 1H NMR (300 MHz, MeOH-d4): δ 9.95 (s, 1H), 8.48 (bs, 1H), 8.22 (s, 1H), 7.63 (d, 8.5 Hz, 1H), 7.53 (dd, 8.5, 1.7 Hz, 1H). MS m/z: 212 (M−1). Analysis calcd. for C10H6NOF3; C, 56.35; H, 2.84, N, 6.57; found, C, 56.60; H, 2.92; N, 6.55.
Workup
- additionThe mixture was poured on ice-water (300 g)
- extractionextracted with EtOAc
- washthe extracts were washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated
- customThe crude product was purified by flash chromatography on silica gel using 10% MeOH/CHCl3 as eluent
- customRecrystallization
- dissolutionby dissolving yellow solid in hot MeOH
- additionpouring onto cold water
Sources & evidence
- ORD record
- ord-317bfb45dc2946bead47257aba4cd1a5
- Source dataset
- uspto-grants-2007_10
- Patent number
- US07285558B2
Reaction notes
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