Hydrochloric Acid → cis-1,3-Dibenzyl-2-imidazolidone-4,5-dicarboxylic acid

HRID 1596752Notes

Reaction equation

HRID 1596752 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][NH:8][CH:9]([C:22]([OH:24])=[O:23])[CH:10]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.[OH-].[K+].Cl[C:28](OC1C=CC=CC=1)=[O:29].Cl>O1CCCC1.O>[O:29]=[C:28]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@@H:10]([C:11]([OH:13])=[O:12])[C@@H:9]([C:22]([OH:24])=[O:23])[N:8]1[CH2:7][C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium Hydroxide2×HCID 15891Phenyl chloroformate2×HCID 108349D-Aspartic acid, N-(phenylmethyl)-3-((phenylmethyl)amino)-, (3S)-rel-2×

Product 1

HCID 9841512cis-1,3-Dibenzyl-2-imidazolidone-4,5-dicarboxylic acidYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

220 g (0.67 mol) of meso-2,3-bis(benzylamino)succinic acid were placed under a nitrogen atmosphere in a 2 l flask fitted with two dropping funnels, a pH electrode, and a stirrer. The meso-2,3-bis(benzylamino)succinic acid was then suspended, while stirring, in 800 ml of tetrahydrofuran and 400 ml of deionized water and brought into solution by the addition of 108 ml of a 50% potassium hydroxide solution. 200 ml of 2.4 mole q. phenyl chloroformate were added dropwise to the solution within 3.5 hours. The pH was maintained between 9 and 11 during the addition of phenyl chloroformate by the successive addition of a 50% potassium hydroxide solution, and the internal temperature was maintained between 30° C. and 35° C. After the addition was completed, the mixture was stirred at about 30° C. for 2 hours and the pH was adjusted to about 7-8 with concentrated hydrochloric acid. The aqueous solution was then extracted twice with toluene and 500 ml of tetrahydrofuran were added to the combined aqueous phases. The mixture was adjusted to a pH of 1.0 with 37% hydrochloric acid and the aqueous phase was separated off. 400 ml of toluene were added to the tetrahydrofuran phase and the tetrahydrofuran was distilled off under reduced pressure. The remaining water was removed azeotropically with toluene. The residual brownish, oily solution was seeded and the crystalline solid was filtered off and washed twice with toluene. After drying to constant weight under reduced pressure, there were obtained 181.5 g (76% yield) of 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid, with a melting point of 172.8° C.

Workup

  1. customfitted with two dropping funnels
  2. temperaturethe internal temperature was maintained between 30° C. and 35° C
  3. additionAfter the addition
  4. extractionThe aqueous solution was then extracted twice with toluene and 500 ml of tetrahydrofuran
  5. additionwere added to the combined aqueous phases
  6. customthe aqueous phase was separated off
  7. addition400 ml of toluene were added to the tetrahydrofuran phase
  8. distillationthe tetrahydrofuran was distilled off under reduced pressure
  9. customThe remaining water was removed azeotropically with toluene
  10. filtrationthe crystalline solid was filtered off
  11. washwashed twice with toluene
  12. customAfter drying to constant weight under reduced pressure

Sources & evidence

ORD record
ord-24af591d1f3c438089bcca97b9f5972a
Source dataset
uspto-grants-2001_09
Patent number
US06291681B1

Reaction notes

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