Potassium Phosphate, Tribasic → HCID 86703557, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 5-chloro-2-fluoro-4-((8-methyl-1,4- dioxaspiro[4.5]decan-8-yl)-methoxy)benzoate (0.28 g, 0.67 mmol), cyclopropylboronic acid (0.08 g, 1.00 mmol), potassium phosphate (0.57 g, 2.68 mmol) and tricyclohexylphosphine tetrafluoroborate (0.05 g, 0.14 mmol) in toluene (3 mL) and water (0.3 mL) under a nitrogen atmosphere was added palladium acetate (0.016 g, 0.07 mmol). The reaction mixture was heated at 130° C. for 30 minutes in the microwave and then cooled to ambient temperature. Water (20 mL) was added and the mixture extracted with ethyl acetate (2×15 mL), the combined organics were washed with brine (10 mL); dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) afforded tert-butyl 5-cyclopropyl-2-fluoro-4-((8-methyl-1,4-dioxaspiro[4.5]-decan-8-yl)methoxy)benzoate (0.28 g, 0.67 mmol) which was used directly into the next step. To a solution of this compound (0.28 g, 0.67 mmol) in dichloromethane (5 mL), was added trifluoroacetic acid (0.5 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then directly purified by column chromatography (0 to 30% ethyl acetate in hexanes) to afford the title compound (0.071 g, 28%). 1H NMR (300 MHz, CDCl3) δ 7.40 (d, J=8.3 Hz, 1H), 6.51 (d, J=12.5 Hz, 1H), 3.85-3.76 (m, 2H), 2.58-2.29 (m, 4H), 2.06-1.73 (m, 5H), 1.55 (s, 9H), 1.28 (s, 3H), 0.91-0.82 (m, 2H), 0.64-0.57 (m, 2H).

Provenance & Evidence