Potassium Carbonate → 3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]-2,2-dimethyl1-propanol fumarate

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Reaction Steps

A mi(xture of 4-(6-fluoro-1,2- benzisoxazol-3-yl)piperidine (3.0 g 13.6 mmol), K2CO3 (12.5 g, 17.5 mmol), 3-bromo-2,2-dimethyl-1-propanol (3 g, 21 mmol, 1.5 eq.) tetra-butylammonium hydrogen sulfate (1 g, phase transfer catalyst) in water (5 ml) and acetonitrile (150 ml) was heated at reflux for 43 days. TLC showed a small spot for the expected product. The mixture was diluted with EtOAc (400 ml) and washed with brine. The organic solution was dried and concentrated to a dark brown mixture. The crude mixture was purified carefully by flash chromatography (SiOc2, 95 g to afford the dried pure product; 260 mg, (6%) as an oil. This oil was converted to the fumarate salt by treatment with fumaric acid (98.5 mg 1.0 eq.) in ethanol . Recrystallization from ethanol:ether yielded 210 mg of white crystals, m.p.=141-145° C.

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