Benzyl Bromide → 1-Benzyl-3-(2-chloro-5-fluoro-phenyl)-5-isopropyl-imidazolidine-2,4-dione

HRID 1092359Notes

Reaction equation

HRID 1092359 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[CH:12]([CH:15]([CH3:17])[CH3:16])[NH:11][C:10]1=[O:18].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[H-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[CH2:19]([N:11]1[CH:12]([CH:15]([CH3:16])[CH3:17])[C:13](=[O:14])[N:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[Cl:1])[C:10]1=[O:18])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 574956373-(2-Chloro-5-fluoro-phenyl)-5-isopropyl-imidazolidine-2,4-dione

Product 1

HCID 574956381-Benzyl-3-(2-chloro-5-fluoro-phenyl)-5-isopropyl-imidazolidine-2,4-dioneYield 76.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

This compound was synthesized in analogy to example 155 (step A to E). In step A, 2-methyl-propionaldehyde was starting material in place of cycloheptanone and ammonium acetate in place of cyclopropylamino acetate. In step B, 2-chloro-5-fluoro-phenyl amine was used in place of 4-Amino-benzoic acid ethyl ester. The pure 3-(2-chloro-5-fluoro-phenyl)-5-isopropyl-imidazolidine-2,4-dione that resulted from this procedure was then benzylated by stirring of 300 mg (1.11 mmol) of 3-(2-Chloro-5-fluoro-phenyl)-5-isopropyl-imidazolidine-2,4-dione with 141 ml (1.16 mmol) of benzyl bromide and 51 mg (1.16 ml) of sodium hydride (55% in oil) in 5 ml DMF for 3 h at RT. The reaction mixture was then taken up in ethyl acetate and was washed with 1N HCl and water. The crude product was purified by silica gel chromatography with Ethyl acetate/Heptane 1:3 to give 306 mg of pure 1-benzyl-3-(2-chloro-5-fluoro-phenyl)-5-isopropyl-imidazolidine-2,4-dione that was reduced with the same procedure described in step D and E to give pure 3-benzyl-1-(2-chloro-5-fluoro-phenyl)-4-isopropyl-imidazolidin-2-one as a colorless viscous oil MS (ESI): 347.3 (MH+).

Workup

  1. washwas washed with 1N HCl and water
  2. customThe crude product was purified by silica gel chromatography with Ethyl acetate/Heptane 1:3

Sources & evidence

ORD record
ord-55d4c61bd53b487694147716f9463ee7
Source dataset
uspto-grants-2012_03
Patent number
US08129423B2

Reaction notes

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