Trifluoroacetic acid → N,N-dimethyl-1-(piperidin-4-yl)-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide

Participants

Reaction Conditions

Reaction Steps

The tert-butyl 4-(1′-(dimethylcarbamoyl)-2′,3′-dihydro-1′H-spiro[piperidine-4,4′-quinoline]-1-yl)piperidine-1-carboxylate 2ad (1.34 g, 2.93 mmol) was dissolved in 40 mL anhydrous dichloromethane and cooled to 0° C. The rapidly stirring solution was treated with TFA (20 mL) and allowed to come to room temperature over 2 hours. The reaction was diluted with ˜20 mL acetonitrile and concentrated to an oil. The oil was brought up in 100 mL 1.0 N HCL and washed with diethyl ether (3×30 mL). The aqueous solution was then basified with 5 N NaOH and the product extracted into dichloromethane (3×50 mL). The organic layer was washed with brine (100 mL), dried over Na2SO4, filtered and concentrated to yield N,N-dimethyl-1-(piperidin-4-yl)-2′,3′-dihydrospiro[piperidine-4,4′-quinoline]-1′-carboxamide 2ae as a colorless oil. LC/MS (10-99% CH3CN/0.05% TFA gradient over 5 min): m/z 357.2, retention time 0.78 minutes. 1H NMR (400 MHz, DMSO-d6) δ 7.35 (d, J=7.8 Hz, 1H), 7.06 (t, J=7.3 Hz, 1H), 6.90 (t, J=7.5 Hz, 1H), 6.75 (d, J=8.0 Hz, 1H), 3.40 (t, J=5.8 Hz, 2H), 3.13 (d, J=12.4 Hz, 2H), 2.77 (s, 6H), 2.71-2.61 (m, 5H), 2.42 (t, J=10.8 Hz, 3H), 1.92 (t, J=10.7 Hz, 2H), 1.86-1.78 (m, 5H), 1.58-1.45 (m, 4H).

Provenance & Evidence