Reacción #553477

Ecuación de reacción

sodium borohydride

methoxydiethylborane

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

acetic acid

→

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

Disolventes

ethyl acetate

tetrahydrofuran

tetrahydrofuran

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction is cooled to -97° C.
2. 2
   TemperaturaThe reaction is 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 is 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 is concentrated by vacuum distillation

Procedimiento

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.

Fuente