Tetrabutylammonium Fluoride → (R)-3-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-3-methyl-[1,4]oxazepan-5-one

Temperatur

0 °C

N-[(R)-1-(5-Bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-chloro-N-(4-methoxy-benzyl)-propionamide (2.08 g, 3.63 mmol) was dissolved in tetrahydrofurane (45 ml) and the solution cooled to 0° C. A solution of tetrabutylammonium fluoride (1 N in tetrahydrofuran, 7.25 ml) was added and the reaction mixture left to warm to room temperature. After 16 hours, the solvent was evaporated at reduced pressure, the residue dissolved in ethyl acetate (25 ml) and water (25 ml) and the mixture stirred for 15 minutes at room temperature. The aqueous layer was separated and extracted with ethyl acetate (50 ml). The organic layers were washed with brine (25 ml), combined, dried over sodium sulfate and evaporated at reduced pressure. After chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 20/10 as the eluent, (R)-3-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-3-methyl-[1,4]oxazepan-5-one (intermediate C10A) was obtained as a white foam (1.34 g, 88% of theory). MS (ISP): m/z=422.1, 424.2 [M+H]+.

1. waitthe reaction mixture left
2. temperatureto warm to room temperature
3. customthe solvent was evaporated at reduced pressure
4. dissolutionthe residue dissolved in ethyl acetate (25 ml)
5. customThe aqueous layer was separated
6. extractionextracted with ethyl acetate (50 ml)
7. washThe organic layers were washed with brine (25 ml)
8. dry with materialdried over sodium sulfate
9. customevaporated at reduced pressure

ORD-Eintrag

ord-399e0a9246d345678dbb9ccc97c79310

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08673894B2