Reacción #447213

Ecuación de reacción

methoxydiethylborane

acetic acid

sodium borohydride

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

→

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

Disolventes

tetrahydrofuran

ethyl acetate

methanol

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction is cooled to -97° C.
2. 2
   TemperaturaThe reaction is maintained between -93° C. and -97° C. for 13 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 500 mL methanol
6. 6
   Concentraciónconcentrated by vacuum distillation
7. 7
   workup.DISSOLUTIONredissolved with 500 mL methanol
8. 8
   workup.DISTILLATIONreconcentrated by vacuum distillation
9. 9
   Otroto give a dark brown oil
10. 10
    Filtraciónfiltered through a plug of silica gel with the aid of 250 mL of ethyl acetate The solution
11. 11
    Otrois evaporated

Procedimiento

Crude (R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3oxohexanoate, 21 g (0.0924 mol), is dissolved in 940 mL of tetrahydrofuran and 190 mL of methanol under a nitrogen atmosphere. This solution is cooled to -85° C. and 95 mL of a 15% solution of methoxydiethylborane in tetrahydrofuran is added. The reaction is cooled to -97° C. and 6.5 9 (0.172 mol) of sodium borohydride is added in 0.5 g portions over 1.5 hours. The reaction is maintained between -93° C. and -97° C. for 13 hours and allowed to warm to room temperature and stand for 60 hours under a nitrogen atmosphere. The reaction is quenched by the addition of 25 mL (0.395 mol) acetic acid and concentrated by vacuum distillation to an oil. The residue is dissolved with 500 mL methanol, concentrated by vacuum distillation, redissolved with 500 mL methanol and reconcentrated by vacuum distillation to give a dark brown oil. This oil is taken up in 500 mL of ethyl acetate and filtered through a plug of silica gel with the aid of 250 mL of ethyl acetate The solution is evaporated to give 15 g of crude [R-(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate which is used without further purification.

Fuente