Hydrochloric Acid → 1'-(4-Methoxy-3-(trifluoromethyl)benzoyl)spiro[chroman-2,4'-piperidin]-4-one

Participants

Reaction Conditions

Reaction Steps

1-(2-Hydroxyphenyl)ethanone (1.80 g, 13.3 mmol) was added portion wise at 25° C. to pyrrolidine (2.20 mL, 26.6 mmol) followed by portion-wise addition of 1-(4-methoxy-3-(trifluoromethyl)benzoyl)piperidin-4-one (4.00 g, 13.3 mmol). Anhydrous methanol (868 μL) was then added and the red slurry was heated at 80° C. for 3 hours. The reaction was cooled to 25° C. and was stirred overnight. Ethyl acetate (5 mL) and 1M HCl (aq, 5 mL) were added. The aqueous layer was separated and discarded. 1M NaOH (aq, 5 mL) was added and the aqueous layer was separated and discarded. A brine solution was added (10 mL) and the aqueous layer was separated and discarded. The organic layer was dried over Na2SO4, filtered and the solvent was evaporated to provide an oil. The crude oil was dissolved in dichloromethane and was purified by column chromatography using 0-50% ethyl acetate/hexanes to provide 1′-(4-methoxy-3-(trifluoromethyl)benzoyl)spiro[chroman-2,4′-piperidin]-4-one (4.4 g, 79%) as a off-white solid. ESI-MS m/z calc. 419.4, found 420.2 (M+1)+. Retention time: 2.63 minutes (4 min run).

Provenance & Evidence