Carbon Dioxide → (S)-3-tert-butoxycarbonylamino-5-methyl-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carboxylic acid cyclopropylmethyl ester

HRID 1374561Notes

Reaction equation

HRID 1374561 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]1[C:14](=[O:15])[N:13]([CH3:16])[C:12]2[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:22](=[O:24])=[O:23].Br[CH2:26][CH:27]1[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH:27]1([CH2:26][O:23][C:22]([N:10]2[CH2:9][C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:21])[C:14](=[O:15])[N:13]([CH3:16])[C:12]3[CH:17]=[CH:18][CH:19]=[CH:20][C:11]2=3)=[O:24])[CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 57617767(S)-tert-Butyl (1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)carbamate

Product 1

HCID 69042563(S)-3-tert-butoxycarbonylamino-5-methyl-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carboxylic acid cyclopropylmethyl esterYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 350 mg (1.2 mmol) of (S)-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-carbamic acid tert-butyl ester [Example 56 a)] in 10 ml of N,N-dimethylformamide was treated successively with about 1 g of solid carbon dioxide, 237 mg (1.7 mmol) of bromomethyl-cyclopropane, and 626 mg (1.9 mmol) of cesium carbonate. The reaction mixture was stirred in a sealed flask at 80° C. during the weekend. For the working-up, the solvent was evaporated under reduced pressure and the residue was dissolved in a mixture of 30 ml of ethyl acetate and 10 ml of water. The organic layer was separated, dried over sodium sulphate and evaporated under reduced pressure. For the purification, the crude compound was chromatographed on silica gel using a 3:1-mixture of heptane and ethyl acetate as the eluent. There were obtained 410 mg (87% of theory) of the (S)-3-tert-butoxycarbonylamino-5-methyl-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carboxylic acid cyclopropylmethyl ester as a white gum; MS: m/e=579 (M+OAc)+.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in a mixture of 30 ml of ethyl acetate and 10 ml of water
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulphate
  5. customevaporated under reduced pressure
  6. customFor the purification
  7. customthe crude compound was chromatographed on silica gel using a 3

Sources & evidence

ORD record
ord-7eb59541883f4e50aa04ab5318ed3ea1
Source dataset
uspto-grants-2007_01
Patent number
US07166587B2

Reaction notes

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