Tetrahydrofuran → 4-(3-Chloro-phenyl)-2-(6-formyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid ethyl ester

HRID 1667761Notes

Reaction equation

HRID 1667761 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:12]2[CH:17]=[C:16]([CH:18]=[O:19])[CH:15]=[CH:14][C:13]=2[N+:20]([O-])=O)=[N:8][C:7]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1)=[O:5])[CH3:2].[Cl-].[NH4+].O1CCC[CH2:33]1>[Zn]>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([N:11]2[C:12]3[CH:17]=[C:16]([CH:18]=[O:19])[CH:15]=[CH:14][C:13]=3[N:20]=[CH:33]2)=[N:8][C:7]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 866428364-(3-Chloro-phenyl)-2-(5-formyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid ethyl ester

Product 1

HCID 866428374-(3-Chloro-phenyl)-2-(6-formyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst2×

Procedure

To mixture of 3.0 g of 4-(3-chloro-phenyl)-2-(5-formyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid ethyl ester (VI.41b), 40 mL of tetrahydrofuran and 20 mL of saturated ammonium chloride solution, was added in three equal portions, at 30 minute intervals, 9 g of zinc powder. After the third portion of zinc powder was added, the orange color disappeared and the mixture turned clear. The solid was removed by filtration. The organic layer was separated. The aqueous layer was extracted twice with 30 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 stirred with 30 mL of acetic acid and 3 mL of trimethyl orthoformate for 1 hour. The mixture was concentrated under reduced pressure, 100 mL of water was and the pH adjusted to 9 by addition of 15% sodium hydroxide solution. The precipitate was collected by filtration and purified by silica gel chromatography, eluting with methanol-dichloromethane (gradient 0:100-2:98) to give 2.3 g of 4-(3-chloro-phenyl)-2-(6-formyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid ethyl ester (I.41a) as an off-white solid.

Workup

  1. customThe solid was removed by filtration
  2. customThe organic layer was separated
  3. extractionThe aqueous layer was extracted twice with 30 mL of dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. concentrationThe mixture was concentrated under reduced pressure, 100 mL of water
  9. additionthe pH adjusted to 9 by addition of 15% sodium hydroxide solution
  10. filtrationThe precipitate was collected by filtration
  11. custompurified by silica gel chromatography
  12. washeluting with methanol-dichloromethane (gradient 0:100-2:98)

Sources & evidence

ORD record
ord-c3df48d0e6eb4bc987d417e6f2bdf8f8
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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