Ammonia → HCID 68552689, compound

Participants

Reaction Steps

A solution of 1-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)-2-(4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanone (825 mg, 1.832 mmol) in DCM (5 mL) was treated with ammonia (9.16 mL of a 2.0 M solution in EtOH, 18.32 mmol) and stirred at RT in a sealed flask for 20 min. The flask was then charged with titanium(IV) isopropoxide (2.163 mL, 7.33 mmol) and re-sealed. The reaction mixture was stirred at RT for 16 h before being treated with sodium borohydride (0.259 mL, 7.33 mmol) in small portions. The resulting mixture was stirred at RT for 30 min, after which time the mixture had become thick and foamy. DCM (5 mL) was added to the reaction mixture in order to facilitate stirring and the reaction continued for an additional 1.5 h. After this time, the mixture was treated with concentrated ammonium hydroxide (10 mL) and DCM (15 mL), stirred vigorously at RT for 20 min and then filtered through Celite. The filtrate was placed in a separatory funnel and the phases were separated. The aqueous phase was extracted with DCM, and the combined DCM extracts were dried (Na2SO4) and concentrated on a rotary evaporator to give the crude product. The crude product was purified by flash chromatography (40 g silica gel cartridge; 40% EtOAc/Hex used to elute the less polar materials; 3% MeOH in EtOAc used to elute the amine) to afford 1-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)-2-(4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanamine (500 mg, 1.108 mmol, 60% yield) as a clear gum. LC-MS: 451.19, [M+H]+; tR=3.07 min (b).

Provenance & Evidence