반응 #1002714

ord-78a36a85e2134b5fafdcd0e5a7a7db51

반응 조건

온도
90°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도Allow the mixture to cool over 8 hours
  2. 2
    workup.WAITThe reaction is complete in about an hour
  3. 3
    기타Partition the mixture between methylene chloride (600 mL) and water (1 L)
  4. 4
    추출Extract the aqueous portion with an additional portion of methylene chloride (400 mL.)
  5. 5
    여과Filter the organic solution through a 300 mL silica plug
  6. 6
    세척wash with 500 mL methylene chloride, 1200 mL ethyl acetate and 1500 mL acetone
  7. 7
    농축Combine appropriate fractions and concentrate

실험 절차

Add 6-bromo-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline (22.7 g, 45 mmol) to a mixture of sodium acetate (19 g, 230 mmol) and the palladium catalyst [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (850 mg, 1.04 mmol) in 130 mL methanol. Place the mixture under 50 psi carbon monoxide atmosphere and stir while warming to 90° C. over 1 hour and with constant charging with additional carbon monoxide. Allow the mixture to cool over 8 hours, recharge again with carbon monoxide and heat to 90° C. The pressure may rise to about 75 PSI. The reaction is complete in about an hour when the pressure is stable and tic (1:1 toluene/acetone) shows no remaining bromide. Partition the mixture between methylene chloride (600 mL) and water (1 L). Extract the aqueous portion with an additional portion of methylene chloride (400 mL.) Filter the organic solution through a 300 mL silica plug and wash with 500 mL methylene chloride, 1200 mL ethyl acetate and 1500 mL acetone. Discard, the acetone portion. Combine appropriate fractions and concentrate to yield 18.8 g (87.4%) of the desired subtitled intermediate as a pink powder.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07265225B2uspto-grants-2007_09