反应详情

To a solution of methyl 5-(3,5-difluorophenyl)-2,2-dimethyl-5-oxopentanoate from Intermediate 1, Step D (500 mg of 85% purity, 1.85 mmol) and (S)-2-methylpropane-2-sulfinamide (336 mg, 2.78 mmol) in THF (9.5 mL), was added titanium tetraethoxide (904 mg, 3.70 mmol). The reaction vessel was quickly sealed and placed into a 60° C. bath for 2 hours. After cooling to ambient temperature the reaction mixture was then diluted with saturated brine (9.5 mL) while experiencing rapid stirring. The resultant slurry was filtered through celite, washing with EtOAc, as needed. The combined organics were then washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of MeOH:CH2Cl2-0.5:99.5 to 3:97, to give the title compound. MS: m/z=374 (M+1).

1. customThe reaction vessel was quickly sealed
2. customplaced into a 60° C.
3. customfor 2 hours
4. filtrationThe resultant slurry was filtered through celite
5. washwashing with EtOAc
6. washThe combined organics were then washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give an oil
11. customThis oil was purified by silica gel chromatography
12. washeluting with a gradient of MeOH