Acetic Acid → methyl 5-bromo-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoate

Participants

Reaction Steps

To a mechanically stirred solution of methyl 5-bromo-2-methyl-3-((tetrahydro-2H -pyran-4-yl)amino)benzoate (15.3 g, 46.6 mmol) and acetaldehyde (7.90 mL, 140 mmol) in 1,2-dichloroethane (DCE) (150 mL) under nitrogen was added acetic acid (16.01 mL, 280 mmol). After 30 min, sodium triacetoxyborohydride (29.6 g, 140 mmol) was added to the reaction mixture. The reaction was stirred overnight, at which time the nitrogen was removed and acetaldehyde (7.90 mL, 140 mmol) was added. After 2 h, the reaction mixture was diluted with water and Na2CO3 (sat′d) and extracted with EtOAc (3×). The ethyl acetate layers were dried over Na2SO4, filtered, and concentrated to obtain methyl 5-bromo-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoate (17.8 g, 50.0 mmol, 107% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.61 (d, J=2.02 Hz, 1 H), 7.54 (d, J=2.27 Hz, 1 H), 3.89-3.73 (m, 5 H), 3.26 (td, J=11.56, 1.89 Hz, 2 H), 3.15-2.86 (m, 3 H), 3.36 (s, 3 H). 1.66-1.55 (m, 2 H), 1.55-1.36 (m, 2 H), 0.79 (t, J=6.95 Hz, 3 H). MS(ES) [M+H]+ 358, 356.

Provenance & Evidence