Indole → 1-Methylindole

To a solution of indole product from Example 38, Step F (182 mg, 0.694 mmol) and dimethyl oxalate (90 mg, 0.76 mmol) in DMF (5 mL), potassium tert-butoxide (86 mg, 0.76 mmol) was added in one portion at room temperature under nitrogen. The reaction mixture was warmed to reflux under nitrogen for 30 min and then was cooled to room temperature. The mixture was diluted with water (50 mL) and extracted (3×) with methylene chloride. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography (SiO2, EtOAc/hexanes, 1:1) to afford the N-methyl indole product, Example 37, as a white solid (180 mg, 92%): mp 106-108° C.; 1H NMR (500 MHz, CDCl3) δ7.19-7.28 (m, 5H), 7.05 (d, J=8.5 Hz, 1H), 7.03 (d, J=3.0 Hz, 1H), 6.73 (d, J=8.5 Hz, 1H), 6.41 (dd, J=3.0, <1 Hz, 1H), 4.37 (t, J=6.3 Hz, 1H), 4.00 (d, J=15.1 Hz, 1H), 3.85 (d, J=15.1 Hz, 1H), 3.75 (s, 3H), 3.08 (dd, J=11.4, 5.4 Hz, 1H), 2.66 (dd, J=11.4, 8.1 Hz, 1H), 2.50 (S, 3H); CI MS m/z=277 [C19H20N2+H]+; IR (KBr) 3050, 2939, 2783, 1487, 1451 cm−1; Anal. Calcd for C19H20N2-0.1 H2O: C, 82.04; H, 7.32; N, 10.07. Found: C, 82.06; H, 7.50; N, 9.85.

1. temperatureThe reaction mixture was warmed
2. temperatureto reflux under nitrogen for 30 min
3. extractionextracted (3×) with methylene chloride
4. washThe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by chromatography (SiO2, EtOAc/hexanes, 1:1)

ORD record

ord-44561715b63e433e92d31bc473ad218a

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07419985B2