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

Participants

Reaction Conditions

Reaction Steps

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

Provenance & Evidence