Hydrochloric Acid → HCID 11607562, compound

Participants

Reaction Conditions

Reaction Steps

A 20 mL round bottom flask equipped with a magnetic stirrer, reflux condenser with nitrogen inlet and thermocouple was charged with (4R,5S)-4-(4-bromophenyl)-2-(2,6-difluorophenyl)-5-methyl-4,5-dihydro-1,3-oxazole (100 mg, 0.284 mmol), 4-(trifluoromethoxy)benzeneboronic acid (70 mg, 0.341 mmol), sodium carbonate (60 mg, 0.566 mmol), tetrakis(triphenylphosphine)palladium(O) (20 mg, 0.017 mmol) and ethyl alcohol (4 mL). The reaction mixture was heated to 78° C. for 7 hours and then cooled to 25° C. and stirred for 16 hours. 1N aq HCl (1 mL) and water (10 mL) were added, and the aqueous layer was extracted with diethyl ether (2×20 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. Column chromatography (4:1 hexane:diethyl ether) afforded the product (38 mg, 31% yield) as a gummy solid: 1H NMR (CDCl3) δ 7.63-7.54 (m, 4H), 7.48-7.38 (m, 1H), 7.35 (d, 2H, J=8.4 Hz), 7.28 (d, 2H, J=8.4 Hz), 7.01 (t, 2H, J=8.1 Hz), 5.55 (d, 1H, J=9.9 Hz), 5.18 (m, 1H), 1.03 (d, 3H, J=6.6 Hz); EI/MS 433 m/e (M+); Chiracel OJ HPLC column shows 74% ee.

Provenance & Evidence