Ethyl orthoformate → 2-(6-Benzyloxy-benzoimidazol-1-yl)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester

HRID 1667730Notes

Reaction equation

HRID 1667730 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:12]2[CH:17]=[C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:15]=[CH:14][C:13]=2[NH2:26])=[N:8][C:7]=1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=1)=[O:5])[CH3:2].[CH:34](OCC)(OCC)OCC>C(O)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([N:11]2[C:12]3[CH:17]=[C:16]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:15]=[CH:14][C:13]=3[N:26]=[CH:34]2)=[N:8][C:7]=1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 866428312-(2-Amino-5-benzyloxy-phenylamino)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester

Product 1

HCID 674458212-(6-Benzyloxy-benzoimidazol-1-yl)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of the 2-(2-amino-5-benzyloxy-phenylamino)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester (VII.25) from previous step, 50 mL of acetic acid, 5 mL of triethyl orthoformate was heated to 50 degrees for 1 hour. The mixture was concentrated under reduced pressure and the residue taken up in 200 mL of dichloromethane. The mixture was washed with 100 mL saturated sodium bicarbonate. The aqueous layer was extracted twice 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 triturated with diethyl ether to afford 3.5 g of 2-(6-benzyloxy-benzoimidazol-1-yl)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester (I.25a) as an off-white solid.

Workup

  1. temperaturewas heated to 50 degrees for 1 hour
  2. concentrationThe mixture was concentrated under reduced pressure
  3. washThe mixture was washed with 100 mL saturated sodium bicarbonate
  4. extractionThe aqueous layer was extracted twice with 100 mL of dichloromethane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-d9131ec0fc3f49a3ac7b17b02d98cbc0
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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