Methyl iodide → 1,4,6-Trimethyl-1H-indole

A solution of the 4,6-dimethylindole (750 mg, 5.2 mmol) in DMF (20 mL) was cooled to 0° C. under nitrogen and treated with 60% sodium hydride in mineral oil (413 mg, 10.3 mmol). After stirring for 15 minutes, iodomethane (0.4 mL, 6.2 mmol) was introduced and the cooling bath was removed (reaction became light purple). After 30 minutes the solution was subsequently quenched with water (5 ml) and then concentrated to reduce the volume of DMF. The reaction was poured into water (200 mL) and EtOAc (100 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×200 mL). The combined organics were washed with water (3×) and then dried (MgSO4), filtered and concentrated. The residue was purified by silica gel flash column chromatography with 10% EtOAc in Hexane as the eluent to afford the title compound (700 mg, 80%) as a white solid.

1. customthe cooling bath was removed
2. custom(reaction became light purple)
3. customAfter 30 minutes the solution was subsequently quenched with water (5 ml)
4. concentrationconcentrated
5. additionThe reaction was poured into water (200 mL) and EtOAc (100 mL)
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with EtOAc (3×200 mL)
8. washThe combined organics were washed with water (3×)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by silica gel flash column chromatography with 10% EtOAc in Hexane as the eluent

ORD record

ord-8b4b3d2dfcde4571ba55fada67167487

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062056B2