Archive for September 2008
Selective cleavage of Arylacetates to Phenols
Morpholine (1.1 mL, 0.012 mol) was added to a solution of ethyl 4-(6-acetoxy-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)butanoate in 10 mL THF and the resulting mixture was refluxed for 1 h. The progress of the reaction was monitored by thin layer chromatography (TLC). The reaction mixture was evaporated, diluted with ethyl acetate, washed with water, dried over sodium sulfate and evaporated under reduced pressure to give ethyl 4-(6-hydroxy-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)butanoate, isolated as a brown oil (1.2 g, 99% yield, NMR complies).
Baeyer-Villager Oxidation
To a mixture of 4-(6-acetyl-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)butanoate (1.3 g, 0.003 mol), urea hydrogen peroxide (0.85 g, 0.009 mol) and sodium bicarbonate (0.76 g, 0.009 mol) in anhydrous dichloromethane (10 mL) under nitrogen atmosphere at ice-bath temperature was added trifluoroacetic anhydride (0.8 mL, 0.006 mol) drop-wise over a period of 10 minutes. The reaction mixture was gradually warmed to room temperature and stirred for 24 h. The reaction mixture was diluted with 50 mL dichloromethane and washed with saturated sodium bicarbonate solution (50 mL), dried over sodium sulfate and evaporated under reduced pressure to give ethyl 4-(6-acetoxy-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)butanoate, isolated as a pale yellow oil (1.36 g, 99% yield, NMR complies).
DIBAL Reduction of Ester to Alcohol
(E)-Ethyl 3-(2-chlorophenyl)acrylate (1.5 g, 0.007 mol) was dissolved in 15 mL of anhydrous dichloromethane, cooled to -78 oC and treated with a solution of di-iso-butylaluminum hydride (1.0 M solution in hexane, 21.4 mL, 0.021 mol) over a period of 20 minutes (the solution turned yellow in color). After 1.5 hours total at -78 oC, the reaction was quenched with methanol (15 mL) at -78 oC (the solution became colorless and then a white solid precipitated out), warmed to 23 oC (over 9 hrs) and treated with a saturated aqueous solution of NH4Cl (60 mL). The resulting mixture was extracted with dichloromethane (2 × 100 mL) (emulsion formed was filtered over Celite to remove white gummy precipitate). The combined extracts were dried (Na2SO4) and concentrated under vacuum to give (E)-3-(2-chlorophenyl)prop-2-en-1-ol which was purified by column chromatography (silica gel, 0-50% ethyl acetate in hexanes) as a pale brown oil (0.45 g, 37% yield, NMR complies). 0.8 g of starting ester was also recovered. Ref: WO2005/097744
