Sodium chloroacetate → 5-Chloro-2-(chloromethyl)-1-[3-(methylsulfonyl)propyl]-1H-benzimidazole

HRID 1500843Notes

Reaction equation

HRID 1500843 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]([CH2:17][CH2:18][CH2:19][S:20]([CH3:23])(=[O:22])=[O:21])[C:10](=O)OC(C)(C)C.[Cl:24][CH2:25]C([O-])=O.[Na+]>Cl>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]2[N:9]([CH2:17][CH2:18][CH2:19][S:20]([CH3:23])(=[O:22])=[O:21])[C:10]([CH2:25][Cl:24])=[N:1][C:2]=2[CH:7]=1

Participants

4

Reactant 2

HCID 23665759Sodium chloroacetateHCID 89923659Tert-butyl 2-amino-4-chlorophenyl(3-(methylsulfonyl)propyl)carbamate

Product 1

HCID 618081805-Chloro-2-(chloromethyl)-1-[3-(methylsulfonyl)propyl]-1H-benzimidazoleYield 44%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 2-amino-4-chlorophenyl(3-(methylsulfonyl)propyl)carbamate (320 mg, 0.92 mmol) and sodium chloroacetate (130 mg, 1.1 mmol) in 4 N HCl was heated to 100° C. After overnight stirring, the reaction solution was cooled to RT and concentrated. The residue was diluted with DCM (100 mL) and washed with sat. NaHCO3 (50 mL). The organic layer was dried and concentrated under vacuum. The residue was purified by prep-TLC (DCM/EtOAc=3:1) to give 5-chloro-2-(chloromethyl)-1-(3-(methylsulfonyl)propyl)-1H-benzo[d]imidazole (130 mg, yield: 44%) as pale solid. MS obsd. (ESI+) [(M+H)+]: 321.0.

Workup

  1. temperaturethe reaction solution was cooled to RT
  2. concentrationconcentrated
  3. additionThe residue was diluted with DCM (100 mL)
  4. washwashed with sat. NaHCO3 (50 mL)
  5. customThe organic layer was dried
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by prep-TLC (DCM/EtOAc=3:1)

Sources & evidence

ORD record
ord-f546e6ba87dd442a95836d5b46375dab
Source dataset
uspto-grants-2015_12
Patent number
US09206191B2

Reaction notes

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