Dimethylformamide → Methyl 3-Amino-4-methoxybenzoate

Participants

Reaction Steps

A 100 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 2 (1.6 g, 5.5 mmol) and N,N-dimethyl formamide (10 mL). 1,8-diazabicyclo[5.4.0]undec-7-ene (0.91 mL, 6 mmol) was added followed by 2,4-difluorobenzyl bromide (0.77 mL, 6 mmol). The reaction mixture was stirred at 60 C for 4 h, was poured into saturated aqueous NaHCO3 and was extracted with ethyl acetate. The organic layer was washed with brine, dried with Na2SO4 and concentrated in vacuo to give the title compound as an orange foam (2.13 g, 93%), which was carried on to the next reaction without further purification. 1H NMR (400 MHz, CD3OD) δ 8.17 (dd, J=2.64 and 11.6 Hz, 1H), 7.82 (td, J=2.7 and 6.8 Hz, 1H), 7.57 (m, 1H), 7.29 (d, J=11.6 Hz, 1H), 7.02 (m, 2H), 6.16 (m, 1H), 6.03 (d, J=3.5 Hz, 1H), 5.14 (s, 2H), 3.89 (s, 6H), 1.93 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ −111.43 (1 F), −116.04 (1 F) ppm. ES-HRMS m/z 416.1310 (M+H calcd for C22H20F2NO5 requires 416.1304). Step 4 Preparation of methyl 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methoxybenzoate

Provenance & Evidence