Acetic Acid → HCID 19081127, compound

HRID 963460Notes

Reaction equation

HRID 963460 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]([NH:13][CH:14]1[N:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[F:27])[C:18]2[CH:28]=[CH:29][CH:30]=[CH:31][C:17]=2[NH:16][C:15]1=[O:32])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:34][C:35]([O:37][CH3:38])=[O:36].C(O)(=O)C>CN(C)C=O.O>[CH2:3]([O:10][C:11]([NH:13][CH:14]1[N:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[F:27])[C:18]2[CH:28]=[CH:29][CH:30]=[CH:31][C:17]=2[N:16]([CH2:34][C:35]([O:37][CH3:38])=[O:36])[C:15]1=[O:32])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 13953699HCID 13953699, compound

Product 1

HCID 19081127HCID 19081127, compoundYield 106.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (0.294g of a 60 % dispersion in mineral oil (7.36 mmol) in N,N-dimethylformamide (20 ml) was added slowly (3RS)-3-benzyloxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (2.70 g) under cooling in an ice-bath. The mixture was stirred at the same temperature for 0.5 hour and at ambient temperature for 1 hour. To the mixture was added dropwise a solution of methyl bromoacetate (1.13 g) in N,N-dimethylformamido (5 ml) under cooling in an ice-bath. The mixture was stirred at ambient temperature overnight. To the reaction mixture was added acetic acid (1 ml) and stirred for 0.5 hour. The resultant was poured into water (100 ml) and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford (3RS)-3-benzyloxycarbonylamino-2,3-dihydro-5-(2-fluoro-phenyl)-1-(methoxycarbonylmethyl)-1H-1,4-benzodiazepin-2-one (3.4 g).

Workup

  1. temperatureunder cooling in an ice-bath
  2. temperatureunder cooling in an ice-bath
  3. stirringThe mixture was stirred at ambient temperature overnight
  4. stirringstirred for 0.5 hour
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-13ad7ce91937467085ef81e34aba4ddc
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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