Acetyl chloride → 2-Hydroxy-4,4-dimethylpentanoic acid

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Reaction Steps

A solution of (±)-4,4-dimethyl-2-hydroxypentanoic acid (f) (40.0 g, 0.274 mol) is prepared in acetyl chloride (70.0 mL, 0.984 mol) and stirred at room temperature for 2 hours. The solution is concentrated (40° C., 20 mm Hg), the residue dissolved in dichloromethane (300 mL), and treated sequentially with oxalyl chloride (30.0 mL, 0.344 mol) and dimethylformamide (0.2 mL, 3 mmol). After stirring overnight at room temperature, the solution is concentrated (40° C., 20 mm Hg), stirred in dichloromethane (400 mL), and treated with N,N-diisopropylethylamine (120 mL, 0.689 mol), dimethylaminopyridine (0.50 g, 4.1 mmol), and (R)-(−)-4-phenyl-2-oxazolidinone (50.0 g, 0.306 mol), resulting in a gentle reflux. After stirring overnight at room temperature, the mixture is washed with hydrochloric acid (1 N, 2×500 mL). The aqueous layer is extracted with dichloromethane (100 mL) and the organic layers are washed with sodium chloride (saturated aqueous, 200 mL), dried (magnesium sulfate), filtered, and the filtrate evaporated (40° C., 20 mm Hg) to provide 100 g of the crude diastereomers as a paste. The paste is divided into two 50 g portions and chromatographed on silica gel [1 kg, 100 mm column, 4:1:1 tert-butyl methyl ether/dichloromethane/hexanes] to provide 42.5 g of oxizolidinone (h) as a colorless solid (47%). An analytical sample is prepared by recrystallizing 0.78 g from 40 mL of 1:1 tBuOMe/hexanes to afford 0.61 g of pure (h) as white needles.

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