Acetic Acid → 1,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

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Crude (5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo-hexanoate (Example 4), approximately 52 mol, was dissolved in 90 L of tetrahydrofuran and 19 L of methanol under a nitrogen atmosphere. This solution was cooled to -85° C. and 24 L of a 50% solution of methoxy-diethylborane in tetrahydrofuran was added. The reaction was cooled to -97° C. and 3.6 kg (126 mol) of sodium borohydride was added in 0.2 kg portions over 3 hours. The reaction was maintained between -93° C. and -85° C. for 5 hours and allowed to warm to room temperature and stand for 10 hours under a nitrogen atmosphere. The reaction was quenched by the addition of 7.5 L (118.5 mol) acetic acid and concentrated by vacuum distillation to an oil. The residue was dissolved with 40 L of methanol, concentrated by vacuum distillation, redissolved with 44 L of methanol, and reconcentrated by vacuum distillation to give a brown oil. This oil was taken up in 90 L of ethyl acetate and washed with 30 L of deionized water. The ethyl acetate solution was concentrated by vacuum distillation to give the title compound, [R-(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate, which was used without further purification.

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