Reacción #67887

Ecuación de reacción

tert-butyl-lithium

(R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyloxy)cyclopent-2-enone

copper cyanide

methyllithium

(S)-tert-butyl(1-iodooctan-3-yloxy)dimethylsilane

→

(2R,3R,4R)-2-(3-(benzyloxy)benzyl)-4-tert-butyldimethylsilyoxy-3-((S)-3-tert-butyldimethylsilyoxyoctyl)cyclopentanone

Disolventes

ether

ether

ether

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaA 25 ml two-necked flask was flame
2. 2
   Otrodried
3. 3
   Temperaturato be cooled
4. 4
   workup.ADDITIONadded to the reaction flask
5. 5
   OtroThe reaction was quenched with 40 ml saturated ammonium chloride (aq)
6. 6
   workup.ADDITIONcontaining 0.4 ml ammonium hydroxide
7. 7
   Otroseparated
8. 8
   Extracciónthe aqueous layer was extracted with ethyl acetate
9. 9
   Secadodried over anhydrous magnesium sulfate
10. 10
    FiltraciónThe solid was filtered off
11. 11
    OtroThe solvent was evaporated off under vacuum
12. 12
    OtroThe crude product was purified by chromatography on silica gel using
13. 13
    workup.ADDITIONa mixture of hexane and ethyl acetate as a gradient eluent

Procedimiento

A 25 ml two-necked flask was flame dried and allowed to be cooled. (S)-tert-butyl(1-iodooctan-3-yloxy)dimethylsilane (1.18 g, 3.2 mmol) and 11.8 L ether were added to the reaction flask, followed by dropwise addition of tert-butyl-lithium (3.75 ml, 1.7M in pentane) at −70° C. A homogenous solution of copper cyanide (0.29 g, 3.2 mmol) and methyllithium (1.6 ml, 2M in ether) in 5.8 ml ether was cooled from room temperature to −70° C. and added to the reaction flask while stirring for 30 minutes. Then, a solution of (R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyloxy)cyclopent-2-enone (0.65 g, 1.6 mmol) in 6.5 ml ether at −70° C. was added to the reaction mixture for 30 minutes. The reaction was quenched with 40 ml saturated ammonium chloride (aq) containing 0.4 ml ammonium hydroxide. The reaction mixture was phase separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off. The solvent was evaporated off under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent. Yield of the titled compound was 1.1 g (85%).

Fuente