Acetic Acid → 2-Methoxy-N-methylbenzylamine

To a solution of 2-anisaldehyde (5.56 g, 40 mmol) in methanol (40 mL) was added methylamine (40 wt % solution in water, 6.9 mL, 80 mol) and acetic acid (240 mg, 4 mmol). The reaction mixture was stirred at room temperature for 16 hours and then cooled in an ice bath. To this ice-cooled mixture was added sodium borohydride (1.51 g, 40 mmol) in portions. The reaction mixture was stirred at room temperature for 3 hours. Most of the solvent was removed under the reduced pressure. The residue was diluted with water (100 mL) and ethyl acetate (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate twice. The combined extracts were washed with brine, dried over sodium sulfate and concentrated to provide the desired 2-methoxybenzyl methylamine (4.7 g, 79%): 1H NMR (CDCl3, 500 MHz) δ 7.23 (d, J=7.4 Hz, 2H), 6.91 (t, J=7.4 Hz, 1H), 6.86 (d, J=7.9 Hz, 1H), 3.83 (s, 3H), 3.75 (s, 2H), 2.42 (s, 3H); ESI MS m/z=152 [M+H]+. This crude product was used in the next step without further purification.

1. temperaturecooled in an ice bath
2. stirringThe reaction mixture was stirred at room temperature for 3 hours
3. customMost of the solvent was removed under the reduced pressure
4. additionThe residue was diluted with water (100 mL) and ethyl acetate (100 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with ethyl acetate twice
7. washThe combined extracts were washed with brine
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated

ORD record

ord-befb41145f044cc681ddd9ec2c0bba1d

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08741901B2