Hydrochloric Acid → 1-Methylindole

The indole product from Example 56 (100 mg, 0.36 mmol) and dimethyl oxalate (46 mg, 0.39 mmol) in DMF (3 mL) were treated with potassium t-butoxide (44 mg, 0.39 mmol). The reaction was heated at reflux for 30 min. Reaction was cooled to room temperature and diluted with water (25 mL). Following extractions (3×) with ethyl acetate, the organic layers were washed with water, brine, dried over sodium sulfate, filtered and concentrated. The dark residue was chromatographed (SiO2, 20% EtOAc/hexanes), and the resulting oil was treated with 1 M HCl (1 eq) in diethyl ether to provide the N-methyl indole product as a white solid (45 mg, 11%): mp 255-258° C.; 1H NMR (300 MHz, CD3OD) δ 7.43-7.25 (m, 3H), 7.12-7.00 (m, 2H), 6.99 (d, J=10.0 Hz, 1H), 6.70 (d, J=8.6 Hz, 1H), 6.50 (d, J=3.1 Hz, 1H), 4.80-4.67 (m, 2H), 3.89 (dd, J=5.6, 11.9 Hz, 1H), 3.81 (s, 3H), 3.65-3.55 (m, 1H), 3.30-3.29 (m, 1H), 3.14 (s, 3H); IR (KBr) 3424, 2944, 2479, 1590, 1449 cm−1; CI MS m/z=295 [C19H19FN2+H]+.

1. temperatureThe reaction was heated
2. temperatureat reflux for 30 min
3. customReaction
4. extractionextractions (3×) with ethyl acetate
5. washthe organic layers were washed with water, brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe dark residue was chromatographed (SiO2, 20% EtOAc/hexanes)

ORD record

ord-1d54f206fd54438aa4bfe831729f91ea

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07309789B2