cis-1,3-Dibenzyl-2-imidazolidone-4,5-dicarboxylic acid → (3AS,6aR)-1,3-dibenzyltetrahydro-1H-furo(3,4-d)imidazole-2,4-dione

HRID 597595Notes

Reaction equation

HRID 597595 reaction equation
[CH2:1]([N:8]1[C@H:12]([C:13]([OH:15])=O)[C@H:11]([C:16]([OH:18])=O)[N:10]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:9]1=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[CH2:19]([N:10]1[C@H:11]2[CH2:16][O:18][C:13](=[O:15])[C@H:12]2[N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9]1=[O:26])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

3

Reactant 1

HCID 9841512cis-1,3-Dibenzyl-2-imidazolidone-4,5-dicarboxylic acid

Product 1

HCID 119819(3AS,6aR)-1,3-dibenzyltetrahydro-1H-furo(3,4-d)imidazole-2,4-dioneYield 98.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of the anhydride of cis-1,3-dibenzyl-2-oxo-imidazolidine-4,5-dicarboxylic acid (50.0 g), (R)-1-phenethylamine (18.9 g) and toluene (200 ml) is stirred and refluxed at 105° to 110° C for 2 hours. The toluene is distilled off, and the resulting residue is heated at 210° to 220° C for 1 hour. cis-1,3-Dibenzyl-5-[(R)-1-phenethyl]-hexahydropyrro[3,4-d]imidazole-2,4,6-trione left as the residue is dissolved in ethanol (750 ml), to which 97 % sodium borohydride (23.3 g) is added below 10° C. The mixture is stirred at room temperature for 16 hours. After the reduction is completed, the mixture is neutralized by the addition of acetic acid (35 ml) and concentrated in vacuo. The residue which contains cis-1,3-dibenzyl-4-[N-(R)-1-phenethylcarbamoyl]-5-hydroxymethyl-tetrahydroimidazol-2-one is heated under reflux with n butanol (500 ml) and 35 % hydrochloric acid (100 ml) for 2 hours. After the reaction is over, the mixture is cooled to room temperature. The n-butanol layer is separated, washed with water and concentrated in vacuo. The precipitate is collected by filtration to yield cis-1,3-dibenzyl-hexahydrofuro[3,4-d]imidazole-2,4-dione (44.6 g, 93.1 %). M.P. 96° to 101° C. [α]D25 + 13.8° (C = 2 in CHCl3). IR (Nujol) 1775, 1690 to 1700 cm-1 (C = 0).

Workup

  1. temperaturerefluxed at 105° to 110° C for 2 hours
  2. distillationThe toluene is distilled off
  3. temperaturethe resulting residue is heated at 210° to 220° C for 1 hour
  4. waitcis-1,3-Dibenzyl-5-[(R)-1-phenethyl]-hexahydropyrro[3,4-d]imidazole-2,4,6-trione left as the residue
  5. dissolutionis dissolved in ethanol (750 ml), to which 97 % sodium borohydride (23.3 g)
  6. additionis added below 10° C
  7. stirringThe mixture is stirred at room temperature for 16 hours
  8. additionthe mixture is neutralized by the addition of acetic acid (35 ml)
  9. concentrationconcentrated in vacuo
  10. temperatureis heated
  11. temperatureunder reflux with n butanol (500 ml) and 35 % hydrochloric acid (100 ml) for 2 hours
  12. customThe n-butanol layer is separated
  13. washwashed with water
  14. concentrationconcentrated in vacuo
  15. filtrationThe precipitate is collected by filtration

Sources & evidence

ORD record
ord-830bae17b57b432197c64a71eb7ed3cb
Source dataset
uspto-grants-1977_03
Patent number
US04014895

Reaction notes

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