Boron trifluoride etherate → 4-(5-Fluoro-3-pyridyl)-4-hydroxy-1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butan-2-one

Participants

Reaction Conditions

Reaction Steps

A solution of 5-fluoronicotinaldehyde (51 mg, 0.41 mmol) in dichloromethane (1.7 mL) was cooled to −78° C. and boron trifluoride diethyl etherate (164 μL, 0.82 mmol) was added. The mixture was stirred at −78° C. for 5 min. The solution from step 1 was added. The mixture was stirred at −78° C. for 5 min, quenched with a buffer solution of pH=7. The aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes to afford 4-(5-fluoro-3-pyridyl)-4-hydroxy-1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butan-2-one (105 mg). 1H NMR (400 MHz, CDCl3) δ 8.46-8.31 (m, 2H), 7.53-7.49 (m, 1H), 7.24-7.22 (m, 2H), 6.83 (d, J=8.1 Hz, 1H), 6.09 (s, 1H), 5.26 (dd, J=8.9, 5.9 Hz, 1H), 4.62-4.53 (m, 1H), 4.13-4.12 (m, 1H), 3.69 (br d, 4H), 3.00 (br s, 2H), 2.88 (d, J=6.2 Hz, 2H), 2.37 (br s, 2H), 2.21 (s, 3H), 1.36 (d, J=6.0 Hz, 6H). ESI-MS m/z calc. 440.21, found 441.4 (M+1)+; Retention time: 1.65 minutes (3 min run).

Provenance & Evidence