Dimethylformamide → HCID 66758946, compound

HRID 1402843Notes

Reaction equation

HRID 1402843 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][CH:6]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)[C:7]([OH:9])=O)[CH3:2].[C:18]([Cl:23])(=O)[C:19](Cl)=O.[CH3:24][N:25]([CH3:28])C=O>ClCCl>[Cl:23][C:18]1[CH:19]=[C:4]2[C:5](=[CH:6][CH:7]=1)[CH2:28][N:25]([C:7](=[O:9])[CH:6]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:17])[CH2:24]2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 66758926HCID 66758926, compound

Product 1

HCID 66758946HCID 66758946, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(4-Chlorophenyl)succinic acid 4-monoethylester (1.11 g) was converted to the corresponding acid chloride by treatment with oxalyl chloride (0.7 ml) in dichloromethane (3 ml) and catalytic amounts of N,N-dimethylformamide (0.5 h at rt, then 0.5 h reflux). All volatiles were removed in vacuo and the crude acid chloride dissolved in dichloromethane (4 ml). This solution was added dropwise to a stirred, ice-cold solution of 5-chloroisoindoline (0.86 g) and triethyl amine (1.7 ml) in dichloromethane (6 ml). After the addition the cooling bath was removed and the solution stirred at rt for 1.5 h. Then the organic layer was diluted with dichloromethane (50 ml), extracted two times with 1M HCl (50 ml), and dried (sodium sulfate). After removal of the solvent the crude was purified by flash chromatography on silica gel (petrol ether/ethyl acetate 2:1) to afford ethyl 4-(5-chloro-2-isoindolinyl)-3-(4-chlorophenyl)-4-oxobutanoate (1.13 g) as amorphous, colourless solid.

Workup

  1. custom0.5 h
  2. customat rt
  3. temperature0.5 h reflux)
  4. customAll volatiles were removed in vacuo
  5. dissolutionthe crude acid chloride dissolved in dichloromethane (4 ml)
  6. additionThis solution was added dropwise to a stirred, ice-cold solution of 5-chloroisoindoline (0.86 g) and triethyl amine (1.7 ml) in dichloromethane (6 ml)
  7. additionAfter the addition the cooling bath
  8. customwas removed
  9. additionThen the organic layer was diluted with dichloromethane (50 ml)
  10. extractionextracted two times with 1M HCl (50 ml)
  11. dry with materialdried (sodium sulfate)
  12. customAfter removal of the solvent the crude
  13. customwas purified by flash chromatography on silica gel (petrol ether/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-3f032cfd8bc04451a36b824433bed821
Source dataset
uspto-grants-2014_12
Patent number
US08912186B2

Reaction notes

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