Sodium hydride → (6-Fluoro-2-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)acetic acid tert-butyl ester

HRID 558950Notes

Reaction equation

HRID 558950 reaction equation
[F:1][C:2]1[C:12]2[NH:11][CH2:10][CH2:9][C:8](=[O:13])[NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>CN(C=O)C.[Cl-].[Na+].O>[C:21]([O:20][C:18](=[O:19])[CH2:17][N:7]1[C:8](=[O:13])[CH2:9][CH2:10][NH:11][C:12]2[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]1=2)([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 231111066-Fluoro-1,3,4,5-tetrahydrobenzo[b][1,4]diazepin-2-one

Product 1

HCID 67000057(6-Fluoro-2-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)acetic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 6-fluoro-1,3,4,5-tetrahydrobenzo[b][1,4]diazepin-2-one from Example 1B (220 mg, 1.2 mmol) in DMF (4 ml) was added sodium hydride (60%, 48 mg, 1.2 mmol) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature and was stirred for 10 min. Tert-butyl bromoacetate (190 μl, 1.2 mmol) was added and the mixture was stirred for 18 h. Brine was added and the mixture was evaporated in vacuo. The residue was partitioned between EtOAc and brine and the organic layer was reduced in vacuo. The residue was purified by flash chromatography on silica (eluant: EtOAc:pet ether 60:40); yield 240 mg, 67%.

Workup

  1. temperaturewhile cooling in an ice/water bath
  2. stirringthe mixture was stirred for 18 h
  3. customthe mixture was evaporated in vacuo
  4. customThe residue was partitioned between EtOAc and brine
  5. customThe residue was purified by flash chromatography on silica (eluant: EtOAc:pet ether 60:40)

Sources & evidence

ORD record
ord-41d3cbdcbd854090b79f7ae3e5353674
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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