Pivaloyl chloride → HCID 44199847, compound

HRID 1642075Notes

Reaction equation

HRID 1642075 reaction equation
[Cl-].C([Al+]CC)C.[C:7]([C:9]1[N:10]=[C:11]2[CH:17]=[CH:16][NH:15][C:12]2=[N:13][CH:14]=1)#[CH:8].[C:18](Cl)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20].C([O-])(O)=O.[Na+]>ClCCl.C(OCC)(=O)C>[C:7]([C:9]1[N:10]=[C:11]2[C:17]([C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:16][NH:15][C:12]2=[N:13][CH:14]=1)#[CH:8]

Participants

7

Reactant 4

HCID 62493Pivaloyl chlorideHCID 516892Sodium BicarbonateHCID 16686102Diethyl aluminum chlorideHCID 57829646HCID 57829646, compound

Product 1

HCID 44199847HCID 44199847, compoundYield 12.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

Diethylaluminum chloride (1.0 M in hexanes, 19.1 mL, 19.1 mmol) was added to a suspension of impure 2-ethynyl-5H-pyrrolo[2,3-b]pyrazine (0.911 g, 6.36 mmol) in 25 mL of dichloromethane at 0-5° C. The mixture was stirred at 0-5° C. for 30 min., then pivaloyl chloride (7.8 mL, 63.6 mmol) was slowly added. The mixture was heated to reflux and stirred for 6 h then cooled to 0-5° C. Sat. Aq. NaHCO3 (50 mL) was carefully added, and the resulting mixture was diluted with 100 mL of ethyl acetate and filtered through a plug of Celite, rinsing with ethyl acetate and water. The filtrate layers were separated, and the aqueous layer extracted with 250 mL of ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated to a residue. Silica gel chromatography (20->60% EtOAc/hexanes) afforded 0.180 g (12%) of 1-(2-ethynyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one as a brown solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. stirringstirred for 6 h
  4. temperaturethen cooled to 0-5° C
  5. filtrationfiltered through a plug of Celite
  6. washrinsing with ethyl acetate and water
  7. customThe filtrate layers were separated
  8. extractionthe aqueous layer extracted with 250 mL of ethyl acetate
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-364278b8658d4431b4fc7da603de2e63
Source dataset
uspto-grants-2012_02
Patent number
US08119636B2

Reaction notes

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