Triethylamine → n-(Cyclopropylmethyl)-2-(1-(2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)piperidin-4-ylidene)acetamide

Participants

Reaction Steps

A solution of TiCl4 (0.0299 ml, 0.271 mmol) in CH2Cl2 (0.5 ml) was added to a solution of N-(cyclopropylmethyl)-2-(piperidin-4-ylidene)acetamide hydrochloride (125 mg, 0.542 mmol) prepared in EXAMPLE 22e, triethylamine (0.225 ml, 1.63 mmol) and 2,2,2,4′-tetrafluoroacetophenone (0.0770 ml, 0.542 mmol) in CH2Cl2 (3.5 ml), and the whole was stirred for 9 hours. A solution of sodium cyanoborohydride (102 mg, 1.63 mmol) in methanol (1 ml) was added to the reaction mixture and the whole was stirred for 30 minutes. After the reaction was quenched with aqueous 2 N NaOH solution (15 ml), the aqueous phase was extracted with ethyl acetate (30 ml×2) and the combined organic phase was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/n-hexane: 35/65 to 55/45) to give N-(cyclopropylmethyl)-2-(1-(2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)piperidin-4-ylidene)acetamide (52 mg, 26%) as a yellow solid: LCMS: 371 {M+1}+. 1H NMR (DMSO-d6)□ δ: 0.11 (m, 2H), 0.37 (m, 2H), 0.85 (m, 1H), 2.17 (m, 2H), 2.43-2.68 (m, 4H), 2.91 (m, 4H), 4.70 (m, 1H), 5.57 (s, 1H), 7.26 (m, 2H), 7.45 (m, 2H), 7.87 (t, 1H).

Provenance & Evidence