Trifluoroacetic acid → Phenylmethyl [(2R,4S)-2-(4-fluoro-2-methylphenyl)-4-(2-propen-1-yl)-4-piperidinyl]carbamate

Participants

Reaction Steps

To a solution of 1,1-dimethylethyl (2R,4S)-2-(4-fluoro-2-methylphenyl)-4-({[(phenylmethyl)oxy]carbonyl}amino)-4-(2-propen-1-yl)-1-piperidinecarboxylate (Intermediate 17 29 g, 60.1 mmol) in dry Dichloromethane (DCM) (500 ml), at 0° C., TFA (125 ml, 1622 mmol) was slowly added in 30 mins and the reaction mixture was stirred for 2 hours at the same temperature. The reaction was diluted with DCM (300 ml) and a saturated solution of NaHCO3 was added until pH=8. Two phases were separated and the aqueous layer was extracted with DCM (200 ml). Combined organic layers were dried (Na2SO4), filtered and evaporated affording the title compound (23.0 g, 60.1 mmol, quantitative yield) as a colourless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.46-7.56 (m, 1H) 7.25-7.41 (m, 5H) 7.07 (br. s., 1H) 6.92-7.03 (m, 2H) 5.67-5.83 (m, 1H) 5.03-5.19 (m, 2H) 4.97 (s, 2H) 3.96 (d, 1H) 2.82-3.03 (m, 2H) 2.76 (d, 2H) 2.29 (s, 3H) 1.99 (d, 2H) 1.54-1.68 (m, 1H) 1.36 (t, 1H); UPLC: Rt=0.62 mins, m/z=383 [M+H]+.

Provenance & Evidence