Dimethylformamide → 3-[5-Chloro-2-(3-methyl-[1,2,4]oxadiazol-5-ylmethoxy)-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To the title compound of Step B (0.15 g, 0.42 mmol) in CH2Cl2 (4 mL) was added DMF (catalytic) and 2M COCl2 in CH2Cl2 (0.3 mL, 0.6 mmol). After 2 h, the reaction was concentrated and THF (2 mL) was added. This solution was added to N-hydroxy-acetamidine (0.035 g, 0.46 mmol) and N,N-diisopropylethylamine (0.065 g, 0.088 mL, 0.50 mmol) in THF (2 mL). The mixture was then heated for 20 min at 155° C. in a microwave reactor, cooled to rt and concentrated. Silica gel chromatography (5-30% EtOAc in hexanes) gave 0.155 g (93%) of the title compound as a clear oil. MS (ESI): mass calcd. for C18H22ClN3O6, 395.1; m/z found, 295.3 [M-100]+. 1H NMR (400 MHz): 6.94 (d, J=8.6 Hz, 1H), 6.91 (dd, J=8.6, 2.2 Hz, 1H), 6.57 (d, J=2.1 Hz, 1H), 5.27 (s, 2H), 4.89-4.85 (m, 1H), 4.32-4.29 (m, 2H), 4.04 (dd, J=10.4, 4.2 Hz, 2H), 2.43 (s, 3H), 1.45 (s, 9H).

Provenance & Evidence