Reacción #697817

Ecuación de reacción

acetic acid

(5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo-hexanoate

methoxy-diethylborane

sodium borohydride

→

1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

Disolventes

tetrahydrofuran

ethyl acetate

tetrahydrofuran

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction was cooled to -97° C.
2. 2
   TemperaturaThe reaction was maintained between -93° C. and -85° C. for 5 hours
3. 3
   Temperaturato warm to room temperature
4. 4
   Concentraciónconcentrated by vacuum distillation to an oil
5. 5
   workup.DISSOLUTIONThe residue was dissolved with 40 L of methanol
6. 6
   Concentraciónconcentrated by vacuum distillation
7. 7
   workup.DISSOLUTIONredissolved with 44 L of methanol
8. 8
   workup.DISTILLATIONreconcentrated by vacuum distillation
9. 9
   Otroto give a brown oil
10. 10
    Lavadowashed with 30 L of deionized water
11. 11
    ConcentraciónThe ethyl acetate solution was concentrated by vacuum distillation

Procedimiento

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.

Fuente