Dimethylformamide → 2-Ethyl-5-methoxyindole-3-carboxaldehyde
Reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([O:17][CH3:18])=[CH:12][CH:11]=2)[CH3:7].CN(C)[CH:21]=[O:22]>>[CH2:6]([C:8]1[NH:9][C:10]2[C:15]([C:16]=1[CH:21]=[O:22])=[CH:14][C:13]([O:17][CH3:18])=[CH:12][CH:11]=2)[CH3:7]Participants
Procedure
Dimethylformamide (1 mL) was cooled to 0° C. Phosphorus oxychloride (0.25 mL) was added and the reaction mixture was stirred for 10 minutes. A solution of 2-ethyl-5-methoxyindole (226 mg, 1.7 mmol) in dimethylformamide (2 mL) was added to the reaction mixture dropwise over 10 minutes. The solution was stirred for an additional 40 minutes. The reaction mixture was added to ice cold 1 N NaOH (25 mL) and stirred for 10 minutes. The precipitate was collected, washed with cold water and dried overnight in a vacuum desiccator set at 40° C. equipped to an oil driven vacuum pump yielding a white solid (213 mg, 62%): TLC Rf 0.55 in 4:1 ethyl acetate/hexanes. Melting point=211-212° C. 1H NMR (600 MHz, CDCl3) δ 11.84 (s, 1H), 10.04 (s, 1H), 7.58 (d, 1H, J=2.4 Hz), 7.30-7.28 (d, 1H, J=9 Hz), 6.81-6.79 (dd, 1H, J1=9 Hz, J2=2.4 Hz), 3.77 (s, 3H), 3.08-3.04 (q, 2H, J=7.8 Hz), 1.33-1.28 (t, 3H, J=7.8 Hz). 13C NMR (150 MHz, CDCl3) δ 183.86, 155.48, 153.86, 130.09, 126.33, 112.68, 112.20, 111.95, 102.41, 55.25, 18.92, 14.54. Elemental analysis calculated for C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.92; H, 6.97; N, 6.34.
Workup
- stirringThe solution was stirred for an additional 40 minutes
- stirringstirred for 10 minutes
- customThe precipitate was collected
- washwashed with cold water
- customdried overnight in a vacuum desiccator
- customset at 40° C.
- customequipped to an oil
Sources & evidence
- ORD record
- ord-f1cab8a408554b93b1e4608bae9abe51
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09023871B2
Reaction notes
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