Ammonium Chloride → HCID 67513649, compound

Participants

Reaction Conditions

Reaction Steps

To a dry and N2 flashed flask was added 4-bromo-3-fluoroanisole (1.04 g, 5.07 mmol) in THF (6 mL) under N2. This was cooled to −78° C., and n-BuLi (1.72 mL, 4.29 mmol) was added. The reaction was stirred at −78° C. for 30 min. The mixture above was added via cannula to a stirred solution of methyl 3-oxocyclobutane carboxylate (500 mg, 3.90 mmol) in dry Et2O (35 mL) at −78° C. under N2. The reaction mixture was allowed to warm to room temperature and was stirred for 1 h. Satd aq. NH4Cl was added and the mixture was stirred until a clear solution resulted. This mixture was extracted with Et2O (3×). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product, which was purified by flash chromatography (Biotage Horizon, 40M, Si, ˜30 mL/min, 100% hexanes for 260 mL, gradient to 40% EtOAc in hexanes over 5184 mL) to afford methyl 3-(2-fluoro-4-methoxyphenyl)-3-hydroxycyclobutanecarboxylate (450 mg, 45%). 1H NMR (500 MHz, CDCl3): δ 7.32 (t, J=8.9 Hz, 1H); 6.69-6.63 (m, 2H); 3.80 (s, 3H); 3.74 (s, 3H); 3.40 (s, 1H); 3.03-2.93 (m, 2H); 2.90-2.82 (m, 1H); 2.67-2.61 (m, 2H).

Provenance & Evidence