Yield:-

Reaction Conditions:

in DMF (N,N-dimethyl-formamide) at 20; for 72 h;

Steps:

97

A solution of bromomethylpyridin-3-yl ketone (4. 55G, 16. 2MMOL) and potassium phthalimide (6. 0g, 32. 4MMOL) in DMF (50mL) was stirred for 3 days at rt before the added to diluted brine (500ML, 1: 1). The solution was made acidic (pH 2) with diluted hydrochloric acid (1M) before washed with ethyl acetate (2 x 100ML). The aqueous layer was then made alkaline (pH 12) again with sodium hydroxide solution (2 M) and extracted with DCM (4 x 200ml). The extracts were combined and dried (MGS04) before concentrated in vacuo. Recrystallisation from methanol (2x) allows to remove crystalline phthalimide and to enrich the title compound in the mother liquer. The crude product was used in Preparation 98 without further purification. ON (d6 DMSO): 5.33 (2H, s), 7.64 (1H, dd), 7.92, 7.97 (4H, 2m), 8.43 (1H, m), 8.88 (1H, m), 9.28 (1H, s); m/z (ES+) = 308.13 [M+ MeCN + H] + ; RT = 2.39min.

References:

WO2004/104001,2004,A2 Location in patent:Page 66-67