Tetrabutylammonium Fluoride → (2RS,5R)-5-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-5-methyl-2-phenyl-morpholin-3-one

Temperature

0 °C

A solution of (RS)-N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-chloro-N-(4-methoxy-benzyl)-2-phenyl-acetamide (1.068 g, 1.68 mmol) in tetrahydrofuran (30 ml) was cooled to 0° C. and treated dropwise during 10 minutes with a solution of tetrabutylammonium fluoride (1 M, 3.36 mmol) in tetrahydrofuran. The orange-colored reaction mixture was stirred at 0° C. for 5 minutes, then for 4 hours at room temperature. For the workup, the reaction mixture was evaporated at reduced pressure, the residue partitioned between water (10 ml) and ethyl acetate (25 ml) and stirred for 15 minutes. The layers were separated and the aqueous layer re-extracted with ethyl acetate (25 ml). The combined organic layers were dried over sodium sulfate and evaporated at reduced pressure. After chromatography on a Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 50/50 as the eluent, the (2RS,5R)-5-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-5-methyl-2-phenyl-morpholin-3-one was obtained as a white foam (369 mg, 45% of theory). Mass (calculated) C25H23BrFNO3 [484.37]; (found) [M+H]+=484, [M+2-H]+=486.

1. waitfor 4 hours at room temperature
2. customFor the workup, the reaction mixture was evaporated at reduced pressure
3. customthe residue partitioned between water (10 ml) and ethyl acetate (25 ml)
4. stirringstirred for 15 minutes
5. customThe layers were separated
6. extractionthe aqueous layer re-extracted with ethyl acetate (25 ml)
7. dry with materialThe combined organic layers were dried over sodium sulfate
8. customevaporated at reduced pressure

ORD record

ord-531d7cee5c654905a313ef0a2ec94337

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188079B2