Acetic Acid → 2-Isopentyl-9-[4-methoxy-3-(trifluoromethyl)benzoyl]-4-phenyl-5-oxa-2,9-diazaspiro[5.5]undecan-3-one

Participants

Reaction Conditions

Reaction Steps

Sodium hydroxide (1.4 mL of 0.2 M, 0.29 mmol) was added to a solution of 2,2,2-trifluoro-N-[[4-hydroxy-1-[4-methoxy-3-(trifluoromethyl)benzoyl]-4-piperidyl]methyl]-N-isopentyl-acetamide (72 mg, 0.14 mmol) in MeOH (722 μL) and the reaction mixture was heated to 65° C. for 16 hours. The solution was partitioned between water (5 mL) and EtOAc (5 mL) and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo to provide the crude amine as a clear oil (54 mg, 92%). ESI-MS m/z calc. 402.4. found 403.7 (M+1)+; Retention time: 1.34 minutes (3 min run). The residue was taken up in THF (480 μL) and added dropwise to a solution of potassium tert-butoxide (36 mg, 0.32 mmol) in tert-butanol (480 μL) and the reaction mixture was heated at 83° C. for 20 minutes. The solution was neutralized with AcOH, and partitioned between water (2 mL) and EtOAc (2 mL), the aqueous layer was extracted with EtOAc (3×2 mL). The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in MeOH (3 mL) and purified by reverse phase HPLC (Gilson) 20-99% water/MeOH to provide 2-isopentyl-9-[4-methoxy-3-(trifluoromethyl)benzoyl]-4-phenyl-5-oxa-2,9-diazaspiro[5.5]undecan-3-one (39 mg, 45%) as a white foam. ESI-MS m/z calc. 518.6. found 519.5 (M+1)+; Retention time: 2.03 minutes (3 min run).

Provenance & Evidence