Hydrochloric Acid → 1H-Furo[3,4-d]imidazole-2,4,6(3H)-trione, dihydro-1,3-bis(phenylmethyl)-, (3aR,6aS)-rel-

HRID 1596753Notes

Reaction equation

HRID 1596753 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][NH:8][CH:9]([C:22]([OH:24])=O)[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:8]([CH2:7][C:4]2[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=2)[C@@H:9]2[C:22]([O:13][C:11](=[O:12])[C@@H:10]2[N:14]1[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:24]

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 106168311H-Furo[3,4-d]imidazole-2,4,6(3H)-trione, dihydro-1,3-bis(phenylmethyl)-, (3aR,6aS)-rel-Yield 78%

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 eq. 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 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 then the pH was adjusted to about 7-8 with concentrated hydrochloric acid. The aqueous solution was 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. After the addition of 700 ml of toluene and 130 ml of acetic anhydride, the mixture was heated to 80° C. After the 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid anhydride had crystallized out, the obtained suspension was cooled to 10° C. within 2 hours in order to complete the crystallization. The crystalline 2-oxo-1,3-dibenzyl-cis4,5-imidazolidinedicarboxylic acid anhydride was filtered off and washed twice with toluene. After drying to constant weight under reduced pressure, there were obtained 173.6 g (78% yield) of 2-oxo-1,3-dibenzyl-cis4,5-imidazolidinedicarboxylic acid anhydride in the form of an analytically pure, colourless solid, with a melting point of 240.2° C. 3.0 g of 2-oxo-1,3-dibenzylamino-cis4,5-imidazolidinedicarboxylic acid anhydride were further obtained on evaporation of the main solution.

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 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. additionAfter the addition of 700 ml of toluene and 130 ml of acetic anhydride
  11. temperaturethe mixture was heated to 80° C
  12. customAfter the 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid anhydride had crystallized out
  13. temperaturethe obtained suspension was cooled to 10° C. within 2 hours in order
  14. customthe crystallization
  15. filtrationThe crystalline 2-oxo-1,3-dibenzyl-cis4,5-imidazolidinedicarboxylic acid anhydride was filtered off
  16. washwashed twice with toluene
  17. customAfter drying to constant weight under reduced pressure

Sources & evidence

ORD record
ord-7844c411832c41b7813219f330272dc4
Source dataset
uspto-grants-2001_09
Patent number
US06291681B1

Reaction notes

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