Triethylamine → (R)-(-)-1-(2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)urea

HRID 1979466Notes

Reaction equation

HRID 1979466 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(N(CC)CC)C.[O:34]=[C:35]1[NH:41][C:40]2[CH:42]=[CH:43][CH:44]=[CH:45][C:39]=2[N:38]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH2:37][C@H:36]1[NH2:52]>O1CCCC1>[O:34]=[C:35]1[NH:41][C:40]2[CH:42]=[CH:43][CH:44]=[CH:45][C:39]=2[N:38]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH2:37][C@H:36]1[NH:52][C:5]([NH:13][C:14]1[CH:26]=[CH:25][CH:24]=[C:16]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[CH:15]=1)=[O:11]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 2737408tert-Butyl-3-aminobenzoateHCID 54463364(R)-(-)-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 54084555(R)-(-)-1-(2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)ureaYield 254.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphosgene (1.8 g) was added to a solution of tert-butyl 3-aminobenzoate (3.13 g) in anhydrous tetrahydrofuran (200 ml) under ice-cooling, and then triethylamine (7.25 ml) was added five times each 1.45 ml over 15 minutes, and the mixture was stirred at room temperature for 5 minutes. Subsequently (R)-(−)-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (4 g) was added under ice-cooling. The mixture was stirred at room temperature for one hour, the reaction mixture was concentrated under reduced pressure. Ice-water was added to the residue, extracted with methylene chloride,the organic layer was washed with saturated brine. After dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. Diisopropyl ether was added to the residue, crystals were collected by filtration, to thereby obtain 7.38 g of the titled compound.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringThe mixture was stirred at room temperature for one hour
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. additionIce-water was added to the residue
  6. extractionextracted with methylene chloride,the organic layer
  7. washwas washed with saturated brine
  8. dry with materialAfter dried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. additionDiisopropyl ether was added to the residue, crystals
  11. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-5a8a17b9b5ae4c708cfdaf91daa6492d
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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