5-chloro-2-(chloromethyl)-1H-1,3-benzodiazole → Ethyl n-[(5-chloro-2-benzimidazolyl)methyl]-n-(4-chlorophenyl)glycinate

HRID 1402832

Reaction equation

HRID 1402832 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:26]=[CH:25][C:19]2[N:20]=[C:21]([CH2:23]Cl)[NH:22][C:18]=2[CH:17]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:15][C:16]1[CH:26]=[CH:25][C:19]2[N:20]=[C:21]([CH2:23][N:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[NH:22][C:18]=2[CH:17]=1

Participants

5

Reactant 3

HCID 2712865-chloro-2-(chloromethyl)-1H-1,3-benzodiazoleHCID 302644Glycine, N-(4-chlorophenyl)-, ethyl esterHCID 516892Sodium Bicarbonate2×

Product 1

HCID 66759582Ethyl n-[(5-chloro-2-benzimidazolyl)methyl]-n-(4-chlorophenyl)glycinateYield 22.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

The mixture of ethyl N-(4-chlorophenyl)glycinate (0.43 g), 5-chloro-2-chloromethylbenzimidazole (0.4 g), and sodium bicarbonate (0.17 g) in N,N-dimethylformamide (2 ml) was stirred at 150° C. for 0.5 h. After cooling to rt the mixture was poured into saturated sodium bicarbonate solution (50 ml) and extracted twice with EtOAc (40 ml). The combined organic layers were washed with 10% sodium carbonate solution (40 ml) and water (40 ml) and dried (sodium sulfate). After concentration the crude (0.66 g) was purified by flash chromatography (dichloromethane/1% methanol) on silica gel to provide an orange solid. The solid was further purified by trituration with diethyl ether to give ethyl N-[(5-chloro-2-benzimidazolyl)methyl]-N-(4-chlorophenyl)glycinate (0.17 g) as a light orange crystals.

Workup

  1. temperatureAfter cooling to rt the mixture
  2. extractionextracted twice with EtOAc (40 ml)
  3. washThe combined organic layers were washed with 10% sodium carbonate solution (40 ml) and water (40 ml)
  4. dry with materialdried (sodium sulfate)
  5. concentrationAfter concentration the crude (0.66 g)
  6. customwas purified by flash chromatography (dichloromethane/1% methanol) on silica gel
  7. customto provide an orange solid
  8. customThe solid was further purified by trituration with diethyl ether

Sources & evidence

ORD record
ord-9831c1577fc64d46b7bb4e74cd716567
Source dataset
uspto-grants-2014_12
Patent number
US08912186B2

Linked notes

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