1,1,2-Trichloroethane → HCID 66759754, compound

Participants

Reaction Steps

A mixture of tert-butyl 3-(6-(methylcarbamoyl)pyridin-3-yl)propanoate (2.16 g, 8.18 mmol), PtO2 (0.40 g) and 1,1,2-trichloroethane (1.0 mL, 12.4 mmol) in methanol (50 mL) was placed in Parr reactor under 70 psi hydrogen atmosphere for 3.5 days. To the mixture was added 1.25 N HCl/MeOH (6 mL, 7.5 mmol) and the reaction was allowed to continue overnight. The reaction was filtered and evaporated to dryness to give tert-butyl 3-(6-(methylcarbamoyl)piperidin-3-yl)propanoate/HCl salt as a foamy solid (2.80 g). LCMS (+APCI) 271 (M+). The solid give tert-butyl 3-(6-(methylcarbamoyl)piperidin-3-yl)propanoate/HCl was mixed with dichloromethane (100 mL) at 0° C. and to this mixture was added DIPEA (diisopropylethylamine) (6.37 mL) and trifluoroacetic anhydride (3.44 g, 16.4 mmol) with stirring for 30 min. The mixture was warmed to room temperature, stirred for 30 min and evaporated to dryness. The crude was neutralized with a saturated aqueous sodium bicarbonate solution (100 mL) and extracted with ethyl acetate. Evaporation gave tert-butyl 3-(6-(methylcarbamoyl)-1-(2,2,2-trifluoroacetyl)piperidin-3-yl)propanoate as an oil that was purified by silica chromatography eluting with a gradient of 5% to 100% EtOAc/Hex then 0% to 10% MeOH/EtOAc to give 0.84 g of the ester as an oil. LCMS (+APCI) 367 (M+1).

Provenance & Evidence