Hydrochloric Acid → 2(R,S)-(methylethyl)-3(R,S)-hydroxytetrahydrothiophene

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Ethyl 3-mercaptopropionate (22.46 g) was dissolved in absolute ethanol (60 mL) and the solution was cooled to -20° C. To it was added sodium ethoxide solution in ethanol (62.5 mL of 21%). A solution of ethyl 2-bromoisovalerate (35 g) in absolute ethanol (60 mL) was added slowly. The reaction mixture was stirred for 2 hours while the reaction temperature was allowed to warm to room temperature. Saturated NH4Cl (150 mL) was added to the reaction mixture and organic layer was separated. The aqueous layer was extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over Na2SO4 and concentrated. Sodium (0.88 g) was dissolved in absolute ethanol (40 mL) at 0° C. and the solution was concentrated. The residue was dissolved in toluene and the product from the previous reaction, Compound 10, (7.78 g) was added. The reaction mixture was heated to reflux for 2 hours. The reaction mixture was cooled to room temperature and 1N HCl was added to the reaction mixture until the pH became acidic. The crude product was extracted with EtOAc (50 mL×3) and the combined organic layers were washed with brine, were dried over Na2SO4 and concentrated. The residue, Compound 11, was heated with 10% H2SO4 (40 mL) at 100° C. overnight. The crude product was extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over Na2SO4 and concentrated. The residue (2(S,R)-(methylethyl)-tetrahydrothiophen-3-one), compound 12, was dissolved in methylene chloride (60 mL) and the solution was cooled to 0° C. Diisobutylaluminumhydride (25 mL, 1M) in methylene chloride was added dropwise. The reaction mixture was stirred for one hour at 0° C. The reaction was quenched by the dropwise addition of water until no gas evolved. 1N HCl (50 mL) was added and the crude product was extracted with methylene chloride (50 mL×3). Combined organic layers were washed with saturated NaHCO3, brine and dried over Na2SO4. Concentration and purification by column chromatography, eluting with 20% ethyl acetate in hexane gave Compound 13, as an oil (1.72 g):

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