Oxalyl chloride → methyl 2-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-2-oxoacetate

HRID 557177Notes

Reaction equation

HRID 557177 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[CH:7]1[C:17]2=[C:18]3[C:13](=[CH:14][CH:15]=[CH:16]2)[CH2:12][CH2:11][CH2:10][N:9]3[CH:8]=1.[CH3:19][O-:20].[Na+]>C(OCC)C.C(OCC)(=O)C>[CH3:19][O:20][C:1](=[O:5])[C:2]([C:7]1[C:17]2=[C:18]3[C:13](=[CH:14][CH:15]=[CH:16]2)[CH2:12][CH2:11][CH2:10][N:9]3[CH:8]=1)=[O:3]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 10942334Sodium MethoxideHCID 156456291-Azatricyclo[6.3.1.0,4,12]dodeca-2,4,6,8(12)-tetraene

Product 1

HCID 59298805methyl 2-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-2-oxoacetateYield 84%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Add oxalyl chloride (1.05 mL, 12.08 mmol) dropwise to a solution of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline (1.67 g, 10.6 mmol) in 150 mL of anhydrous diethyl ether at 0° C. and stir the resulting solution at 0° C. for 40 minutes. Cool the mixture to −78° C. and slowly add sodium methoxide (42 mL, 21 mmol, 0.5 M in methanol). Upon completion of the addition, remove the dry ice bath and allow the reaction to warm to 20-24° C. over 2 hours. Dilute the mixture with ethyl acetate (200 mL), wash with water (100 mL) and separate the layers. Wash the organic layer with saturated aqueous sodium chloride (50 mL), dry over sodium sulfate, filter, and concentrate under reduced pressure. Dissolve the residue in ethyl acetate (100 mL), filter through a 2 inch plug of coarse silica gel, and concentrate under reduced pressure to give the title compound as a yellow solid (2.16 g, 84%).

Workup

  1. temperatureCool the mixture to −78° C.
  2. additionUpon completion of the addition
  3. customremove the dry ice bath
  4. customthe reaction
  5. temperatureto warm to 20-24° C. over 2 hours
  6. washwash with water (100 mL)
  7. customseparate the layers
  8. washWash the organic layer with saturated aqueous sodium chloride (50 mL)
  9. dry with materialdry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate under reduced pressure
  12. dissolutionDissolve the residue in ethyl acetate (100 mL)
  13. filtrationfilter through a 2 inch plug of coarse silica gel
  14. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-05228f1e04fd42beaf329dc7daf53c77
Source dataset
uspto-grants-2011_11
Patent number
US08058425B2

Reaction notes

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