Triethylamine → (R)-(-)-2-methyl-2-[3-[1-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)ureido]phenoxy]propionic acid benzyl ester

HRID 1979455Notes

Reaction equation

HRID 1979455 reaction equation
[CH3:1][C:2]([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=1)([CH3:13])[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].ClC(Cl)(O[C:26](=[O:32])OC(Cl)(Cl)Cl)Cl.C([N:36](CC)CC)C.[C:41]([C:45]([CH2:47][N:48]1[C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=2[N:52]([CH:59]2[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]2)[CH2:51][C@@H:50](N)[C:49]1=[O:66])=[O:46])([CH3:44])([CH3:43])[CH3:42]>O1CCCC1.C(Cl)(Cl)Cl.O>[CH2:6]([O:5][C:3](=[O:4])[C:2]([CH3:1])([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]([C@H:50]2[C:49](=[O:66])[N:48]([CH2:47][C:45]([C:41]([CH3:42])([CH3:44])[CH3:43])=[O:46])[C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=3[N:52]([CH:59]3[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]3)[CH2:51]2)[C:26]([NH2:36])=[O:32])[CH:16]=1)[CH3:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 11190074(R)-1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineHCID 21201793Benzyl 2-methyl-2-(3-aminophenoxy)propionate

Product 1

HCID 69693359(R)-(-)-2-methyl-2-[3-[1-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)ureido]phenoxy]propionic acid benzyl esterYield 178.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
6.5 °C

Procedure

Benzyl 2-methyl-2-(3-aminophenoxy)propionate (200 mg) was dissolved in tetrahydrofuran (5 ml), the solution was cooled to internal temperature 5-8° C. Triphosgene (77 mg) was added, stirred for 5 minutes. Subsequently, triethylamine (0.36 g) was added every 5 minutes after divided into two portions. The mixture was stirred at room temperature for 10 minutes, a solution of (R)-1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (230 mg) in tetrahydrofuran (5 ml) was added to the mixture, stirred for one hour. Water and chloroform were added to the reaction mixture, and extracted. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography(chloroform), to thereby obtain 310 mg of the title compound as pale yellow oil (Yield: 72.4%).

Workup

  1. stirringThe mixture was stirred at room temperature for 10 minutes
  2. stirringstirred for one hour
  3. extractionextracted
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography(chloroform)

Sources & evidence

ORD record
ord-6756c5c7fb174aa7990bb855760fd771
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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