Hydrochloric Acid → (R)-5-(5-amino-2-fluoro-phenyl)-5-methyl-morpholin-3-one

Temperature

105 °C

A solution of (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholin-3-one (building block B) (1.0 g, 3.47 mmol) in toluene (61 ml) was treated with benzophenonimine (1.26 g, 6.94 mmol), tris(dibenzylideneacetone)-dipalladium chloroform complex (108 mg, 0.104 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (147 mg, 0.347 mmol) and sodium tert-butoxide (1.0 g, 10.4 mmol). The mixture was heated to 105° C. and stirred at this temperature for 18 hours. Even though following TLC (silica gel; heptane:ethyl acetate=1:1) the reaction was not completed, the mixture was stirred with hydrochloric acid (1M, 50 ml) for 45 minutes. Solid sodium hydrogen carbonate was added until pH 8 was reached and the mixture was extraced with ethyl acetate. The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The crude material was purified by flash chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 20:80 as the eluent. The (R)-5-(5-amino-2-fluoro-phenyl)-5-methyl-morpholin-3-one was obtained as a dark red oil (312 mg, 40%); (calculated) C11H13FN2O2 [224.24]; (found) [M+H]+=225.

1. dry with materialThe combined organic layers were dried over sodium sulphate
2. customevaporated at reduced pressure
3. customThe crude material was purified by flash chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 20:80 as the eluent

ORD record

ord-be433224200e492bbbb6231833e6bf4a

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242943B2