反应详情

3-[4-(Azetidine-1-carbonyl)-phenoxy]-5-((S)-2-tert-butoxy-1-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide (101.3 μmol; 51.3 mg) was charged to a small screw capped reaction tube. DCM (500.0 μL) was added the reaction mixture followed by TFA (506.3 μmol; 38.3 μL; 57.7 mg), the reaction mixture was stirred at ambient temperature for 18 hours. HPLC analysis showed no reaction after this time. The reaction mixture was heated to 40° C., extra TFA (506.3 μmol; 38.3 μL; 57.7 mg) was added to the reaction tube and the mixture was held at 40° C. for 18 hours. Water (1 mL) was added to the reaction tube followed by sodium hydroxide (2M) (1.0 mmol; 506.3 μL; 526.6 mg). MTBE (4 mL) was added and the mixture was stirred for 5 minutes. An oily gum had formed which was dissolved by addition of EtOAc (2 mL). The two layers were separated and the upper organic layer was retained, the aqueous was extracted again with EtOAc (2×5 mL). The combined organic layers were washed with saturated brine (5 mL), dried over MgSO4, filtered and concentrated in vacuo to give a colourless oil (35 mg, 75.7% yield).

1. customcapped
2. customreaction tube
3. customno reaction after this time
4. temperatureThe reaction mixture was heated to 40° C.
5. waitthe mixture was held at 40° C. for 18 hours
6. stirringthe mixture was stirred for 5 minutes
7. customAn oily gum had formed which
8. customThe two layers were separated
9. extractionthe aqueous was extracted again with EtOAc (2×5 mL)
10. washThe combined organic layers were washed with saturated brine (5 mL)
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo