Benzamide → HCID 66883731, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (3.8 mL, 27 mmol) in THF (85 mL) in a −10° C. bath was added a solution of butyllithium (17.0 mL of a 1.4 M solution in hexane, 23.8 mmol). After stirring at −10° C. for 10 minutes, the cooling bath was further cooled to −78° C. The resulting solution of LDA was then treated with a mixture of N,N-diethyl-5-fluoro-2-methyl-benzamide (3.48 g, 16.6 mmol) and 4-benzyloxy-N-methoxy-N-methylbenzamide (4.51 g, 16.6 mmol) as a solution in THF (25 mL) by cannula addition over ˜8 minutes. The flask and cannula containing the benzamide mixture solution was then rinsed with additional THF (10 mL) which was added to the reaction to insure complete transfer. TLC analysis of the deep purple reaction solution after stirring for 15 minutes at −78° C. showed one main product spot. After stirring for 30 minutes at −78° C. the reaction was quenched by the addition of saturated aqueous NH4Cl (50 mL). The cooling bath was removed and the suspension was allowed to slowly warm to ambient temperature. After warming to ambient temperature, H2O was added to dissolve the solids that had formed, the reaction was diluted with Et2O (400 mL), and transferred to a separatory funnel. The resulting layers were separated, and the aqueous layer was extracted with Et2O (3×75 mL). The organic layers were combined, washed with saturated aqueous sodium chloride (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford a pale yellow oil. The crude oil was purified by silica gel column chromatography eluting with a gradient from 0% to 30% EtOAc/hexane. Product-containing fractions from the column were combined and concentrated to afford 2-[2-(4-benzyloxyphenyl)-2-oxo-ethyl]-N,N-diethyl-5-fluoro-benzamide (4.74 g, 68% yield) as a pale yellow oil. 1H NMR analysis showed some impurities present.

Provenance & Evidence