Dimethyl Sulfate → 1-methyl-1H-indole-7-carbaldehyde

To a solution of 1H-indole-7-carboxaldehyde (20.0 g, 137 mmol) and dimethylsulfate (19.1 g, 151 mmol) in DMF (400 mL) at 0° C. was added a 60% dispersion of NaH in mineral oil (6.60 g, 165 mmol). The reaction was stirred and allowed to warm to room temperature over 30 minutes. The reaction was quenched with H2O, diluted with EtOAc (1 L) and H2O. The two layers were separated and the aqueous layer was extracted with EtOAc (250 mL). The combined organic layers were washed with H2O (3×500 mL), brine, saturated aq LiCl, and brine. The solution was dried (MgSO4), filtered and concentrated to afford the title compound as an off white solid of sufficient quality to use directly in the next step. Flash chromatography (80% hexane/EtOAc) can be used to afford the title compound pure, as a white solid. 1H NMR (400 MHz, DMSO-d6) 10.39 (s, 1H), 7.91 (d, J=7 Hz, 1H), 7.75 (d, J=7 Hz, 1H), 7.42 (d, J=3 Hz, 1H), 7.21 (dd, J=7, 7 Hz, 1H), 6.60 (d, J=3 Hz, 1H), 4.08 (s, 3H). MS (electrospray, m/z) 160 (M++1).

1. customThe reaction was quenched with H2O
2. additiondiluted with EtOAc (1 L) and H2O
3. customThe two layers were separated
4. extractionthe aqueous layer was extracted with EtOAc (250 mL)
5. washThe combined organic layers were washed with H2O (3×500 mL), brine, saturated aq LiCl, and brine
6. dry with materialThe solution was dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-358913c5c987450d96d1c1117e9e1637

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07109229B2