1-Chloroethyl chloroformate → 4-(Azetidin-3-yloxy)-1-benzyl-1,3-dihydro-benzoimidazol-2-one

HRID 730564Notes

Reaction equation

HRID 730564 reaction equation
C([N:14]1[CH2:17][CH:16]([O:18][C:19]2[C:27]3[NH:26][C:25](=[O:28])[N:24]([CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:23]=3[CH:22]=[CH:21][CH:20]=2)[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClC(Cl)C>[NH:14]1[CH2:17][CH:16]([O:18][C:19]2[C:27]3[NH:26][C:25](=[O:28])[N:24]([CH2:29][C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:23]=3[CH:22]=[CH:21][CH:20]=2)[CH2:15]1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 578349704-(1-Benzhydryl-azetidin-3-yloxy)-1-benzyl-1,3-dihydro-benzoimidazol-2-one

Product 1

HCID 160420254-(Azetidin-3-yloxy)-1-benzyl-1,3-dihydro-benzoimidazol-2-oneYield 82.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-(1-Benzhydryl-azetidin-3-yloxy)-1-benzyl-1,3-dihydro-benzoimidazol-2-one (78 mg, 0.17 mmol) was dissolved in 0.33 mL dichloroethane and cooled to 0° C. under nitrogen. α-Chloroethyl chloroformate (0.018 mL, 0.164 mmol) was added dropwise, and the solution was refluxed for 2 hours, concentrated in vacuo, and dissolved in 20 mL methanol. The solution was refluxed for one hour, concentrated in vacuo and dissolved in 75 mL dichloromethane, and the resulting solution was washed with 75 mL 2M aqueous potassium carbonate and 75 mL water. The organic phase was dried over sodium sulfate, concentrated in vacuo and purified by flash (3% methanol in dichloromethane) chromatography to give 42 mg (0.14 mmol, 82%) of 4-(azetidin-3-yloxy)-1-benzyl-1,3-dihydro-benzoimidazol-2-one as a clear oil. MS: 296 (M+H)+. The corresponding hydrochloride salt, prepared by recrystallization from EtOH/HCl, gave a melting point of 181.0-184.0° C.

Workup

  1. temperaturethe solution was refluxed for 2 hours
  2. concentrationconcentrated in vacuo
  3. dissolutiondissolved in 20 mL methanol
  4. temperatureThe solution was refluxed for one hour
  5. concentrationconcentrated in vacuo
  6. dissolutiondissolved in 75 mL dichloromethane
  7. washthe resulting solution was washed with 75 mL 2M aqueous potassium carbonate and 75 mL water
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. custompurified by flash (3% methanol in dichloromethane) chromatography

Sources & evidence

ORD record
ord-ec4a03decfd1465284630c2fd2d53c21
Source dataset
uspto-grants-2009_09
Patent number
US07582760B2

Reaction notes

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