Hydrochloric Acid → methyl (2R,3S)-2,3-epoxy-3-(4-acetoxyphenyl)propionate

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Reaction Steps

To a solution of 20.112 g (94.03 mmol) of sodium metaperiodide in 273 ml of water is added 5.321 g (63.34 mmol) of sodium hydrogencarbonate in small portions with stirring, whereby white salt is precipitated. Acetonitrile (182 ml) and carbon tetrachloride (182 ml) are added to the reaction mixture with stirring. Then 91 mg (0.684 mmol) of ruthenium dioxide and 6.528 g (31.35 mmol) of (2S,3S)-2,3-epoxy-3-(4-acetoxyphenyl)propanol (II) are added at 2°-3° C. Further 13.41 g (62.7 mmol) of sodium metaperiodate and 169 mg of ruthenium dioxide are added to the mixture. The mixture is maintained at pH 6-6.5 by addition of sodium hydrogencarbonate or 1.2N hydrochloric acid and then allowed to stand for 20 hours. After 43 hours from the beginning of the reaction, 19.5 ml of isopropanol is added, and the mixture stirred for 20 minutes, the precipitate removed by filtration and washed with water and chloroform. The filtrate and the washings are combined and the aqueous layer is extracted with chloroform. The aqueous layer is adjusted at pH 1 by portionwise addition of 17.0 g (0.135 mmol) of oxalic acid and extracted with three 120 ml portions of chloroform. The chloroform layer is washed with a chilled aqueous sodium chloride, dried over magnesium sulfate. Triethylamine (4.4 ml) is added, and the solution evaporated in vacuo. The mixture of 10.44 g (124.27 mmol) of powdered sodium hydrogencarbonate in 64 ml of dimethyl formamide is added to the oily residue (12.05 g), stirred for an hour, then 5.5 ml (58.1 mmol) of dimethyl sulfate is added, and the mixture allowed to stand for 2 hours. The reaction mixture is poured into 640 ml of ice water, and seed crystals are added and stirred. The crystalline precipitate is collected by filtration and washed with water. The filtrate is extracted with ethyl acetate and the ethyl acetate solution is washed with water, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The combined crystals and residue are recrystallized from ether/hexane to give 4.509 g of methyl (2R,3S)-2,3-epoxy-3-(4-acetoxyphenyl)propionate (IV) as colorless needles, mp. 67.5°-68° C., [α]D24 : -138.4±1.6° (c 1.130, chloroform). A portion of the compound is further recrystallized from the same solvent system to give pure sample showing mp. 67°-68° C., [α]D23.5 : -140.7±1.8° (c 1.008, chloroform). Anal. Calcd. for C12H12O5 : C;61.01, H;5.12, Found: C;60.74, H;5.18. IR Spectrum: νmax(Nujol): 1760, 1730, 1610, 1599 cm-1. NMR Spectrum (CDCl3, ppm): 7.35(d, J=9 Hz, 2H), 7.08(d, J=9 Hz, 2H), 4.10(d, J=2 Hz, 1H), 3.83(s, 3H), 3.48(d,J=2 Hz, 1H), 2.30(s,3H).

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