تفاعل #67887

ord-07fccfd5bd4c4dcc93af0ec0e0dd9b1c

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

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

الإجراء التجريبي

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%).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08524939B2uspto-grants-2013_09