반응 #73816

ord-244a22b1f1f1491888202153b756c4d7

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타at 0° C.
  2. 2
    온도before cooling again to 0° C.
  3. 3
    기타The aqueous layer was separated
  4. 4
    추출extracted further with ethyl acetate (10 ml)
  5. 5
    세척The combined organic liquors were washed with saturated brine
  6. 6
    건조dried (MgSO4)
  7. 7
    농축concentrating in vacuo
  8. 8
    온도heating to 80° C. for 40 minutes
  9. 9
    기타The organic liquors were separated
  10. 10
    세척washed with further bicarbonate solution (50 ml), hydrochloric acid (2N, 100 ml) and saturated brine (50 ml)
  11. 11
    건조before drying (MgSO4)
  12. 12
    농축concentrating in vacuo
  13. 13
    기타The residue was purified by column chromatography (SiO2)
  14. 14
    세척eluting with ethyl acetate/petrol (5:95) gradient to (15:85)

실험 절차

To a solution of 3-(4-fluorophenyl)-3-(4-bromophenyl)propionic acid* (1.0 g, 3.09 mmol) in acetone (4 ml) at 0° C. was sequentially added triethylamine (561 ul, 4.02 mmol) in acetone (1.6 ml) and ethyl chloroformate (443 ul, 4.64 mmol) in acetone (1.6 ml). The reaction was allowed to warm to room temperature, stirred for 30 minutes before cooling again to 0° C. and sodium azide (402 mg, 6.18 mmol) in water (1.6 ml) was added. The resultant brown solution was stirred for 45 minutes before addition of water (10 ml) and diethyl ether (10 ml). The aqueous layer was separated and extracted further with ethyl acetate (10 ml). The combined organic liquors were washed with saturated brine, dried (MgSO4) and concentrating in vacuo. The residue was dissolved in anhydrous toluene (12 ml) before addition of benzyl alcohol (567 ul, 9.27 mmol) and heating to 80° C. for 40 minutes. The reaction was allowed to cool to room temperature before addition of ethyl acetate (50 ml) and saturated sodium bicarbonate (50 ml). The organic liquors were separated and washed with further bicarbonate solution (50 ml), hydrochloric acid (2N, 100 ml) and saturated brine (50 ml) before drying (MgSO4) and concentrating in vacuo. The residue was purified by column chromatography (SiO2), eluting with ethyl acetate/petrol (5:95) gradient to (15:85) to afford the title compound (594 mg, 45%). LC/MS: (PS-A2) Rt 3.18 No ionisation.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08541461B2uspto-grants-2013_09