Cyclopropanecarbonyl chloride → 3-[7-(Cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl ester

HRID 346895Notes

Reaction equation

HRID 346895 reaction equation
[CH3:1][O:2][C:3](=[O:30])[CH2:4][CH:5]([N:19]1[CH2:27][C:26]2[C:21](=[C:22]([NH2:28])[CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:29])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:15])[F:14])=[C:8]([O:16][CH2:17][CH3:18])[CH:7]=1.[CH:31]1([C:34](Cl)=[O:35])[CH2:33][CH2:32]1>C1COCC1>[CH3:1][O:2][C:3](=[O:30])[CH2:4][CH:5]([N:19]1[CH2:27][C:26]2[C:21](=[C:22]([NH:28][C:34]([CH:31]3[CH2:33][CH2:32]3)=[O:35])[CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:29])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:15])[F:14])=[C:8]([O:16][CH2:17][CH3:18])[CH:7]=1

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 103648123-(7-Amino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl ester

Product 1

HCID 100742223-[7-(Cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the THF solution of 3-(7-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl ester (2.8 g, 7 mmol) was added cyclopropanyl carbonyl chloride (0.72 ml, 8 mmol) dropwise. The reaction mixture was then heated to reflux for 1 hour. The solvent was removed under vacuo. The mixture was dissolved in EtOAc (50 ml) and washed with water (50 ml×2). The organic layer was dried over Na2SO4 and concentrated under vacuo. The resulted solid was stirred with ether (20 ml) for 1 hour and filtered to give a total of 2.5 g (77% yield) white solid which was used in the next step without further purification.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureto reflux for 1 hour
  3. customThe solvent was removed under vacuo
  4. dissolutionThe mixture was dissolved in EtOAc (50 ml)
  5. washwashed with water (50 ml×2)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated under vacuo
  8. filtrationfiltered

Sources & evidence

ORD record
ord-11339839dca34b87b7b8ef562e5b2cc0
Source dataset
uspto-grants-2007_02
Patent number
US07173058B2

Reaction notes

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