Dimethylformamide → 4-(3-Chloro-phenyl)-2-(5-dimethoxymethyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid ethyl ester

HRID 1667759

Reaction equation

HRID 1667759 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH2:11])=[N:8][C:7]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.[CH3:30][O:31][CH:32]([O:43][CH3:44])[C:33]1[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[C:35](F)[CH:34]=1>O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:35]2[CH:34]=[C:33]([CH:32]([O:43][CH3:44])[O:31][CH3:30])[CH:38]=[CH:37][C:36]=2[N+:39]([O-:41])=[O:40])=[N:8][C:7]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 299233212-Amino-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl esterHCID 540322924-Dimethoxymethyl-2-fluoro-1-nitrobenzene

Product 1

HCID 866428354-(3-Chloro-phenyl)-2-(5-dimethoxymethyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid ethyl esterYield 71.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2.82 g (10 mmole) of 2-amino-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester, 9.75 g (30 mmole) of cesium carbonate, 20 mL of dimethylformamide, and 2.15 g (10 mmole) of 4-dimethoxymethyl-2-fluoro-1-nitro-benzene was heated at 80 degrees for 1 hour. The cooled mixture was diluted with 200 mL of water and extracted three times with 100 mL of dichloromethane. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified with silica gel chromatography, eluting with ethyl acetate-hexanes (gradient 0:100-10:90) to give 3.4 g of 4-(3-chloro-phenyl)-2-(5-dimethoxymethyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid ethyl ester (VI.41a) as a yellow solid.

Workup

  1. temperaturewas heated at 80 degrees for 1 hour
  2. extractionextracted three times with 100 mL of dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified with silica gel chromatography
  8. washeluting with ethyl acetate-hexanes (gradient 0:100-10:90)

Sources & evidence

ORD record
ord-f5a88d1bba5b42c598c81d0190bd66a5
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Linked notes

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