Reaktion #1259792

Reaktionsgleichung

6-bromo-4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline

carbon monoxide

dichloromethane

carbon monoxide

carbon monoxide

bromide

sodium acetate

→

desired subtitled intermediate

4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline-6-carboxylic acid methyl ester

Lösungsmittel

toluene acetone

methanol

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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 the (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. MS ES+=385 (M+1).

Quelle