2-Bromo-4-fluoroanisole → Tert-butyl 4-(5-fluoro-2-methoxybenzyl)-4-hydroxypiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction 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 a solution of 1-oxa-6-azaspiro[2.5]octane-6-carboxylic acid, 1,1-dimethylethyl ester (56.2 g) in anhydrous tetrahydrofuran (I 10 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.

Provenance & Evidence