5-FLUORO-2-METHOXYPHENYLMAGNESIUM BROMIDE synthesis

Yield:-

Reaction Conditions:

with isopropylmagnesium chloride in tetrahydrofuran at 30; for 16.5 h;

Steps:

A solution of iso-propylmagnesium chloride in tetrahydrofuran (2M, 130 mL) was added dropwise over 30 minutes to a stirred solution of 2-bromo-4-fluoroanisole (34.2 mL) in anhydrous tetrahydrofuran (400 mL) at 30 °C under nitrogen. After a further 16 hours at 30 °C, copper (I) bromide dimethyl sulphide complex (0.4 g) was added followed by solution of tert-butyl 1-oxa-6-azaspiro [2.5] octane-6-carboxylate (56.2 g) in anhydrous tetrahydrofuran (110 mL). After a further 3 hours at 30 °C, the solution was cooled to 20 °C, diluted with water (600 mL) and extracted with tert.-butyl methyl ether (600 mL) then ethyl acetate (600 mL). Combined organic extracts were dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure to give crude sub-title compound (86 g) as a solid. APCI-MS : m/z 240 [M+H- (CH3) 2CCH2-C02

References:

WO2005/61499,2005,A1 Location in patent:Page/Page column 25-26