Triethylamine → 2,2,2-trifluoro-N-[[4-hydroxy-1-[4-methoxy-3-(trifluoromethyl)benzoyl]-4-piperidyl]methyl]-N-isopentyl-acetamide

Participants

Reaction Steps

Palladium (50.8 mg, 0.48 mmol) 10% on activated carbon and N-[(1-benzyl-4-hydroxy-4-piperidyl)methyl]-2,2,2-trifluoro-N-isopentyl-acetamide (112 mg, 0.29 mmol) in propan-2-ol (3 mL) was stirred under an atmosphere of hydrogen for 18 hours. The catalyst was filtered through Celite® and washed with MeOH. The organics were concentrated in vacuo to provide a clear oil. To the oil was added DMF (2 mL) and triethylamine (40 μL, 0.29 mmol) and this solution was added dropwise to a solution 4-methoxy-3-(trifluoromethyl)benzoic acid (64 mg, 0.29 mmol) and HATU (110 mg, 0.29 mmol) in DMF (1 mL). The reaction mixture was stirred for 16 hours. The solution was partitioned between water and EtOAc and the layers were separated. The aqueous layer was extracted with EtOAc (3×100 mL). The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was taken up in MeOH and purified by reverse phase HPLC (Gilson 20-99% water/MeOH) to give 2,2,2-trifluoro-N-[[4-hydroxy-1-[4-methoxy-3-(trifluoromethyl)benzoyl]-4-piperidyl]methyl]-N-isopentyl-acetamide (82 mg, 56%). ESI-MS m/z calc. 498.5. Found 499.5 (M+1)+; Retention time: 1.86 minutes (3 min run).

Provenance & Evidence