Triphosgene → (R)-(-)-1-(2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonyl-4-methylphenyl)urea

HRID 1979485Notes

Reaction equation

HRID 1979485 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[CH3:13][C:14]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][C:15]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].[O:28]=[C:29]1[NH:35][C:34]2[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=2[N:32]([CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[CH2:31][C@H:30]1[NH2:46]>O1CCCC1.C(N(CC)CC)C>[O:28]=[C:29]1[NH:35][C:34]2[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=2[N:32]([CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[CH2:31][C@H:30]1[NH:46][C:5]([NH:27][C:24]1[CH:25]=[CH:26][C:14]([CH3:13])=[C:15]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH:23]=1)=[O:11]

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 21202027Tert-butyl 5-amino-2-methylbenzoateHCID 54463364(R)-(-)-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 54387510(R)-(-)-1-(2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonyl-4-methylphenyl)ureaYield 256.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Under ice-cooling, triphosgene (456 mg) was added to a solution of tert-butyl 2-methyl-5-aminobenzoate (850 mg) in anhydrous tetrahydrofuran (50 ml), triethylamine (1.85 ml) was added thereto five times each 0.37 ml over a 15 minutes after divided into five portions. After the mixture was stirred at room temperature for 5 minutes, (R)-(−)-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (1.04 g) was added under ice-cooling. The resultant mixture was stirred at room temperature for one hour, the reaction mixture was poured into ice-water, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, crystals so precipitated were washed with diisopropyl ether, to thereby obtain 1.94 g of the title compound (Yield: 98%).

Workup

  1. temperatureUnder ice-cooling
  2. additionwas added
  3. temperaturecooling
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure, crystals
  8. customso precipitated
  9. washwere washed with diisopropyl ether

Sources & evidence

ORD record
ord-4ca6419255e6446eb8f15a210d6a4ccb
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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