Lithium Hexamethyldisilazide → 2-(4-Bromo-2,6-dimethylphenyl)-5-[hydroxy(tetrahydropyran-4-yl)methyl]-3-methoxycyclopent-2-enone

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Reaction Conditions

Reaction Steps

To a solution of 2-(4-bromo-2,6-dimethylphenyl)-3-methoxycyclopent-2-enone (7.5 g, 26.0 mmol) in anhydrous tetrahydrofuran (70 ml) under a nitrogen atmosphere is added lithium bis(trimethylsilyl)amide (44.6 ml, 31.0 mmol, 0.7M in tetrahydrofuran) dropwise at −75°C. After stirring for 40 minutes at this temperature a second solution of tetrahydropyranyl-4-carboxaldehyde (5.90 g, 52.0 mmol) in tetrahydrofuran (70 ml) is added over 20 minutes, and the resulting solution is stirred at −75°C. for 2 hours. After warming to room temperature the mixture is stirred for a further 2 hours, then is quenched with ice cold water (100 ml) and extracted with ethyl acetate (3×150 ml). Organics are combined, dried over sodium sulphate, filtered and the filtrate is concentrated in vacuo to afford 2-(4-bromo-2,6-dimethylphenyl)-5-[hydroxy(tetrahydropyran-4-yl)methyl]-3-methoxycyclopent-2-enone. This material is used directly in the next step without further purification.

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