Cesium carbonate → Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-chloro-2-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

A mixture of bicyclo[4.1.0]heptan-1-ylmethanol (0.86 g, 6.80 mmol), tert-butyl 5-chloro-2,4-difluorobenzoate (1.69 g, 6.80 mmol) and cesium carbonate (4.40 g, 13.7 mmol) in anhydrous dimethylsulfoxide (15 mL) was heated at 100° C. under nitrogen for 16 hours. The reaction mixture was filtered through a pad of diatomaceous earth and rinsed with ethyl acetate (100 mL). The organic layer was washed with 1.0 M hydrochloric acid (20 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to dryness. The residue was purified by column chromatography with a mixture of hexanes in ethyl acetate (9:1) to afford the title compound as a white solid (1.30 g, 54%): 1H NMR (300 MHz, CDCl3) 7.85 (d, J=18.4 Hz, 1H), 6.54 (d, J=12.20 Hz, 1H), 3.81 (d, J=9.1 Hz, 1H), 3.68 (d, J=9.1 Hz, 1H), 1.98-1.79 (m, 4H), 1.39-1.29 (m, 3H), 1.56 (s, 9H), 1.02-0.94 (min, 1H), 0.89-0.83 (m, 1H), 0.67-0.62 (m, 1H), 0.40-0.37 (m, 1H); MS (ES+) m/z 377.2, 379.2 (M+23).

Provenance & Evidence