Water → tert-Butyl 7-chloro-2-oxo-1,2,3,5-tetrahydro-4H-1,4-benzodiazepine-4-carboxylate

HRID 446753Notes

Reaction equation

HRID 446753 reaction equation
C([O:3][C:4](=O)[CH2:5][N:6]([CH2:14][C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[NH2:22])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])C.CC(C)([O-])C.[K+].O.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[C:10]([O:9][C:7]([N:6]1[CH2:14][C:15]2[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=2[NH:22][C:4](=[O:3])[CH2:5]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 23665647Potassium tert-butoxideHCID 67364561HCID 67364561, compound

Product 1

HCID 67377785tert-Butyl 7-chloro-2-oxo-1,2,3,5-tetrahydro-4H-1,4-benzodiazepine-4-carboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [(2-amino-5-chloro-benzyl)-tert-butoxycarbonyl-amino]acetic acid ethyl ester (60 g, 0.18 mol) in tetrahydrofuran (600 ml) was added potassium tert-butoxide (22 g, 0.19 mol) in small portions at 5° C. under cooling on an ice-water batch. After completed addition the cooling bath was removed and reaction mixture was stirred for 3 h at room temperature followed by addition of water (400 ml), saturated aqueous ammonium chloride solution (280 ml) and ethyl acetate (800 ml). After 10 minutes the precipitate was collected by filtration. The layers were separated from the filtrate, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was combined with the precipitate, which had previously been collected by filtration, and crystallized from hot ethyl acetate to give the title compound (46 g, 88%) as white solid. MS m/e: 295 (M−H+).

Workup

  1. additionaddition the cooling bath
  2. customwas removed
  3. customreaction mixture
  4. filtrationAfter 10 minutes the precipitate was collected by filtration
  5. customThe layers were separated from the filtrate
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. filtrationhad previously been collected by filtration
  9. customcrystallized from hot ethyl acetate

Sources & evidence

ORD record
ord-c4f33e92a18044b4a554e5e02e1f8f05
Source dataset
uspto-grants-2013_07
Patent number
US08481528B2

Reaction notes

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