Ethyl bromoacetate → 1-Ethoxycarbonylmethyl-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester

HRID 1253882Notes

Reaction equation

HRID 1253882 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:16][C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[NH:13][C:12](=[O:21])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25].[Cl-].[NH4+]>CCCCCC.CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:16][C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[N:13]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:12](=[O:21])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 22632545tert-Butyl 2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylate

Product 1

HCID 686381191-Ethoxycarbonylmethyl-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl esterYield 72.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (152.6 mg, 3.81 mmol, 60% suspension in mineral oil) was washed with hexane (2×2 mL) in a flame dried round bottomed flask under nitrogen atmosphere. To the resulting free floating powder, was added a solution of 2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester (500 mg, 1.90 mmol) in dry DMF (10 mL) at 0° C. The reaction mixture was stirred at this temperature for 1 h. Ethyl bromoacetate (0.21 mL, 1.9 mmol) was added at 0° C. and the reaction mixture was allowed to come to r.t. and stirred overnight. After the completion of the reaction as confirmed by TLC, reaction mixture was cooled to 0° C. and saturated solution of ammonium chloride (3 mL) was added dropwise to the reaction mixture. The crude product was extracted with ethylacetate (3×10 mL). The combined organic layers were dried over Na2SO4 and solvents were removed in vacuo to afford 1-ethoxycarbonylmethyl-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester (480 mg, 72%) as a viscous oil which was used as such without any further purification for the next step.

Workup

  1. customdried round bottomed flask under nitrogen atmosphere
  2. customto come to r.t.
  3. stirringstirred overnight
  4. customAfter the completion of the reaction
  5. customas confirmed by TLC, reaction mixture
  6. extractionThe crude product was extracted with ethylacetate (3×10 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4 and solvents
  8. customwere removed in vacuo

Sources & evidence

ORD record
ord-8dfb5d86e7c544c287f0e0b87850a4a8
Source dataset
uspto-grants-2013_06
Patent number
US08455479B2

Reaction notes

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