Methyl chloroformate → HCID 11202793, compound

HRID 1271071Notes

Reaction equation

HRID 1271071 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:34]=[CH:33][C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18](=[O:32])[C:19]([NH:21][C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]=[CH:27][CH:26]=[CH:25]4)=[O:20])=[CH:10]2)=[CH:6][CH:5]=1.Cl[C:36]([O:38][CH3:39])=[O:37].CCCCCCC.C(OCC)(=O)C>C1COCC1.O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18](=[O:32])[C:19]([N:21]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]=[CH:27][CH:26]=[CH:25]4)[C:36](=[O:37])[O:38][CH3:39])=[O:20])=[CH:10]2)=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 10203597EntasobulinHCID 21899848Ethylacetate heptane

Product 1

HCID 11202793HCID 11202793, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

930.2 mg (27.3 mMol) of NaH (as a 60% strength dispersion in mineral oil) are added, under nitrogen, to a cooled, stirred solution of 10.0 g (22.7 mMol) of 2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxo-N-quinolin-6-ylacetamide in 500 ml of dry THF. The solution is stirred at 0° C. until a yellow precipitate separates out and, after that, stirred for a further 15 minutes. After that, 2.58 g (27.3 mMol) of methyl chloroformate are added dropwise at a temperature below +5° C. The reaction is monitored by thin layer chromatography (eluent: n-heptane/ethyl acetate 1/1 RF=0.11). The reaction mixture is poured into water and the resulting mixture is extracted with ethyl acetate; the organic phase is washed with a saturated solution of sodium chloride and dried over anhydrous MgSO4. Evaporating off the solvent yields a crude product, which is purified by column chromatography (n-heptane/acetone 2/1) in order to give 3. Thin layer chromatography shows that 3 still contains slight impurities, which can be removed by stirring the crude 3 with acetone for 1 h. Filtration yields 3 as pale yellow crystals.

Workup

  1. stirringafter that, stirred for a further 15 minutes
  2. extractionthe resulting mixture is extracted with ethyl acetate
  3. washthe organic phase is washed with a saturated solution of sodium chloride
  4. dry with materialdried over anhydrous MgSO4
  5. customEvaporating off the solvent
  6. customyields a crude product, which
  7. customis purified by column chromatography (n-heptane/acetone 2/1) in order
  8. customto give 3
  9. customcan be removed
  10. stirringby stirring the crude 3 with acetone for 1 h
  11. filtrationFiltration

Sources & evidence

ORD record
ord-a964567d12404c84b87c6cb3c893e12f
Source dataset
uspto-grants-2007_04
Patent number
US07205299B2

Reaction notes

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