Potassium Phosphate, Tribasic → Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

To a mixture of tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-chloro-2-fluorobenzoate (1.20 g, 3.00 mmol) in toluene (18 mL) was added cyclopropylboronic acid (1.55 g, 18.00 mmol), potassium phosphate tribasic (1.91 g, 9.00 mmol), tricyclohexyl- phosphine tetrafluoroborate (0.884 g, 2.40 mmol), palladium acetate (0.269 g, 1.20 mmol) and water (2 mL). The reaction mixture was thoroughly degassed by passing argon through it and then heated in a microwave at 150° C. for 30 minutes. The reaction was performed 4 times as described. After cooling to ambient temperature, the reaction mixtures were combined, diluted with ethyl acetate (200 mL) and filtered over anhydrous sodium sulfate. After removing all volatiles under reduced pressure, the residue was purified by silica gel column chromatography using 0-30% ethyl acetate in hexanes as eluent to afford the title compound as a yellowish oil (3.16 g, 16%): 1H NMR (300 MHz, CDCl3) δ 7.35 (d, J=8.4 Hz, 1H), 6.48 (d, J=12.7 Hz, 1H), 3.95-3.92 (m, 4H), 3.80 (d, J=6.1 Hz, 2H), 2.04-1.70 (m, 10H), 1.54 (s, 9H), 0.91-0.82 (m, 2H), 0.64-0.57 (m, 2H).

Provenance & Evidence