Benzyl chloroformate → 7-Methoxy-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid benzyl ester

HRID 1041602Notes

Reaction equation

HRID 1041602 reaction equation
C([N:8]1[CH2:14][C:13]2[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[CH:18][C:12]=2[NH:11][C:10](=[O:21])[CH2:9]1)C1C=CC=CC=1.Cl[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]>ClCCl>[CH2:26]([O:25][C:23]([N:8]1[CH2:14][C:13]2[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[CH:18][C:12]=2[NH:11][C:10](=[O:21])[CH2:9]1)=[O:24])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

4

Reactant 2

HCID 10387Benzyl chloroformateHCID 578538974-Benzyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one

Product 1

HCID 672637677-Methoxy-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid benzyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-benzyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (4.67 g, 16.5 mmol) in dichloromethane (150 mL) was added benzyl chloroformate (6.2 g, 36.0 mmol). The mixture was heated to reflux for four hours whereupon LCMS showed completion of the reaction. The mixture was cooled to room temperature, washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered and concentrated. The crude product was purified by flash chromatography over silica gel (0-5% MeOH/DCM) to afford 5.0 g (93%) of 7-methoxy-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid benzyl ester; NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.35 (m, 5H), 7.04 (d, J=9 Hz, 1H), 6.84 (d, J=9 Hz, 1H), 5.08 (s, 2H), 4.54 (s, 2H), 4.20 (2s, 2H), 3.70 (2s, 3H);); MS (m/e) 327 (M+1); mp 138° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for four hours whereupon LCMS
  3. customcompletion of the reaction
  4. washwashed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography over silica gel (0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-356640d925a54e3eb74dabc61c4abae1
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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