Benzyl Bromide → HCID 86647368, compound

HRID 1474110Notes

Reaction equation

HRID 1474110 reaction equation
[CH3:1][N:2]1[CH2:6][C@H:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[NH:4][C:3]1=[O:17].Br[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O>[CH2:19]([N:4]1[C@@H:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:6][N:2]([CH3:1])[C:3]1=[O:17])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 7498Benzyl BromideHCID 50999035HCID 50999035, compound

Product 1

HCID 86647368HCID 86647368, compoundYield 32.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To the solution of (R)-benzyl 1-methyl-2-oxo-imidazolidine-4-carboxylate (1000 mg, 4.27 mmol) in 11 ml of DMF sodium hydride (129 mg, 5.12 mmol) was added, resulting in a slightly exothermic reaction (temperature rise to about 27° C.) and formation of a turbid solution. After stirring for 1 h at room temperature (bromomethyl)benzene (0.609 ml, 876 mg, 5.12 mmol) was added resulting again in a slightly exothermic reaction (temperature rise to about 29° C.). After stirring overnight the reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic layers were washed successively with a 10% citric acid solution, twice with saturated NaHCO3 solution and brine, dried over Na2SO4 and the solvent was then removed under reduced pressure. Column chromatography on silica gel using dichloromethane and dichloromethane/methanol 98/2 gave (R)-benzyl 3-benzyl-1-methyl-2-oxoimidazolidine-4-carboxylate (425 mg, 1.38 mmol, yield: 31%, ESI-MS [M+H]+=325.1), which was converted into to the corresponding carboxylate by stirring overnight at room temperature in a mixture of 2.7 ml of THF and 1.44 mL of 2N NaOH. Water was added to the reaction mixture followed by extraction with MTBE. The aqueous layer subsequently was acidified to pH 3 using 2M HCl, and extracted three times with dichloromethane. The combined organic layers were then washed with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The title compound was obtained as colorless oil which solidified by standing over time (245 mg, yield: 75%).

Workup

  1. customresulting in a slightly exothermic reaction (temperature rise to about 27° C.) and formation of a turbid solution
  2. additionwas added
  3. customresulting again in a slightly exothermic reaction (temperature rise to about 29° C.)
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organic layers were washed successively with a 10% citric acid solution, twice with saturated NaHCO3 solution and brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent was then removed under reduced pressure

Sources & evidence

ORD record
ord-e1a8eb1c427d465d82da988b61b585be
Source dataset
uspto-grants-2015_04
Patent number
US09018206B2

Reaction notes

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