Sodium Hydroxide → HCID 19787833, compound

Participants

Reaction Steps

A solution of 19.74 g (64.42 mmol) of 3-(4-acetoxy -3,5-di-tert-butylphenyl)propanol, 12.68 g (77.3 mmol) of 3-picolylchloride hydrochloride and 5 g of tetrabutylammonium hydrogen sulphate in 250 ml of toluene is treated with 250 ml of 50% aqueous sodium hydroxide with vigorous stirring (>400 rpm) under a nitrogen atmosphere and external cooling with a watdr-bath. Stirring of the dark reaction mixture is continued for an additional 5 hours at room temperature. After usual extractive work-up, the crude product (26.3 g) is purified by flash-chromatography over silica gel with AcOEt/H 2:1 as the eluent, yielding 16.9 g (66%) of 2,6-di-tert-butyl-4-[5-(3-pyridyl)-4-oxapentyl]phenyl acetate as a colourless oil, which is dissolved in 100 ml of dry tetrahydrofuran and added dropwise at -78° C. (acetone/dry ice) under inert conditions to a stirred suspension of 1.77 g (46.76 mmol) lithium aluminium hydride in 100 ml of anhydrous tetrahydrofuran. The reaction mixture is stirred overnight in the gradually-warming cooling bath, maintained for 2 hours at 400C, and quenched under vigorous stirring and external cooling with ice-water by sequential, careful addition of 1.77 g of water, 1.77 g of 15% aqueous sodium hydroxide and a f inal portaionn of 5.31 g of water. After 1 hour, the resulting suspension is diluted with 200 ml of THF, dried with 20 g of Na2SO4 and the aluminate precipitate is removed by filtration through a fritted glass funnel and the solvent evaporated at reduced pressure, to give 12.9 g of crude 2,6-di-tert-buty -1-4-[5-(3-pyridyl)-4-oxapentyl)phenol as a yellow solid, leaving 11.49 g (76% for the deprotection step) of pure product, m.p. 105*C, after recrystallization with n-hexane/ethyl acetate. (C23H33NO2 ; F.W. 355.5).

Provenance & Evidence