反应详情

温度

65 °C

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).

1. customThe solution was partitioned between water (5 mL) and EtOAc (5 mL)
2. extractionthe aqueous layer was extracted with EtOAc (3×5 mL)
3. dry with materialThe combined organics were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto provide the crude amine as a clear oil (54 mg, 92%)
7. customRetention time: 1.34 minutes (3 min run)
8. temperaturethe reaction mixture was heated at 83° C. for 20 minutes
9. custompartitioned between water (2 mL) and EtOAc (2 mL)
10. extractionthe aqueous layer was extracted with EtOAc (3×2 mL)
11. dry with materialThe combined organics were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. dissolutionThe residue was dissolved in MeOH (3 mL)
15. custompurified by reverse phase HPLC (Gilson) 20-99% water/MeOH