Methyl iodide → tert-Butyl 1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylate

HRID 1253878Notes

Reaction equation

HRID 1253878 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].I[CH3:23].[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]([CH3:23])[C:12](=[O:21])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 22632545tert-Butyl 2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylate

Product 1

HCID 68638936tert-Butyl 1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylateYield 90.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (18 mg, 0.45 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 (80 mg, 0.30 mmol) in dry DMF (3 mL) at 0° C. The reaction mixture was stirred at this temperature for 1 h. Iodomethane (0.0.19 mL, 0.30 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 (2 mL) was added dropwise to the reaction mixture. The crude product was extracted with ethyl acetate (2×10 mL). The combined organic layers were dried over Na2SO4 and the solvents were removed in vacuo to afford 1-methyl-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester (75 mg, 89%) 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 ethyl acetate (2×10 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-261322671bf9408ab878e2aa854216f1
Source dataset
uspto-grants-2013_06
Patent number
US08455479B2

Reaction notes

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