L-Phenylalanine → 5-Benzyl-3-(2,5-difluorophenyl)imidazolidine-2,4-dione

HRID 1165686Notes

Reaction equation

HRID 1165686 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]=[C:10]=[O:11].[NH2:12][C@H:13]([C:21]([OH:23])=O)[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:14]([CH:13]1[NH:12][C:10](=[O:11])[N:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[C:21]1=[O:23])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 6140L-PhenylalanineHCID 8471TriethylamineHCID 27332661,4-Difluoro-2-isocyanatobenzene

Product 1

HCID 146505055-Benzyl-3-(2,5-difluorophenyl)imidazolidine-2,4-dioneYield 82.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2,5-Difluorophenylisocyanate (1.55 g, 10.0 mmol) in methylene chloride (25 mL) was added dropwise to a suspension of phenylalanine (1.65 g, 10.0 mmo) in methylene chloride (50 mL) containing triethylamine (1.4 mL, 1.01 g, 10.0 mmol). The solution was allowed to stir overnight, and was then concentrated. The residue was taken up into 6N HCl and heated to reflux for 3 hours. The cooled solution was extracted with ethyl acetate (3×), and the combined extracts where washed with water (2×), dried (over MgSO4), filtered and concentrated to give 2.7 grams. Purification by column chromatography gave 2.5 grams of 5-benzyl-3-(2,5-difluorophenyl)imidazolidine-2,4-dione.

Workup

  1. concentrationwas then concentrated
  2. temperatureheated
  3. temperatureto reflux for 3 hours
  4. extractionThe cooled solution was extracted with ethyl acetate (3×)
  5. washthe combined extracts where washed with water (2×)
  6. dry with materialdried (over MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give 2.7 grams
  10. customPurification by column chromatography

Sources & evidence

ORD record
ord-f4788d490a2d48f7b3a07ec54118ddb7
Source dataset
uspto-grants-1990_03
Patent number
US04911748

Reaction notes

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