Potassium Iodide → Tert-butyl 3-(1-ethoxycarbonyl-3-cyclohexylpropyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

HRID 280958Notes

Reaction equation

HRID 280958 reaction equation
Cl.N[C@@H]1C(=O)NC2C=CC=CC=2OC1.C([O-])(=O)C.[Na+].C1(CCC(=O)C(OCC)=O)CCCCC1.[CH2:35]([O:37][C:38]([CH:40]([NH:49][CH:50]1[C:56](=[O:57])[NH:55][C:54]2[CH:58]=[CH:59][CH:60]=[CH:61][C:53]=2[O:52][CH2:51]1)[CH2:41][CH2:42][CH:43]1[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1)=[O:39])[CH3:36].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:69][C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71].[I-].[K+]>[Ni].O.C(OCC)(=O)C.CN(C)C=O.C(O)(=O)C.C(O)C>[CH2:35]([O:37][C:38]([CH:40]([NH:49][CH:50]1[C:56](=[O:57])[N:55]([CH2:69][C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[C:54]2[CH:58]=[CH:59][CH:60]=[CH:61][C:53]=2[O:52][CH2:51]1)[CH2:41][CH2:42][CH:43]1[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1)=[O:39])[CH3:36]

Participants

14

Reactant 7

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 66052tert-Butyl chloroacetateHCID 517045Sodium AcetateHCID 13454680Ethyl 4-cyclohexyl-2-oxobutanoateHCID 18599716(S)-7-Amino-6,7-dihydro-9H-5-oxa-9-aza-benzocyclohepten-8-one hydrochlorideHCID 233200213-(1-Ethoxycarbonyl-3-cyclohexylpropyl)amino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one

Product 1

HCID 23320010Tert-butyl 3-(1-ethoxycarbonyl-3-cyclohexylpropyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

Reagents, catalysts & solvents 6

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3(S)-amino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one hydrochloride (2 g), ethanol (100 ml), sodium acetate (0.8 g), acetic acid (0.6 g), molecular sieves 4A (5 g) and ethyl 4-cyclohexyl-2-oxo-butyrate (5 g) is catalytically hydrogenated over Raney nickel at room temperature under atmospheric pressure. After the absorption of hydrogen ceases, the catalyst is removed by filtration and the filtrate is evaporated in vacuo. To the residue are added water (50 ml) and ethyl acetate (200 ml), and the mixture is agitated thoroughly. The ethyl acetate layer is dried over anhydrous magnesium sulfate and evaporated in vacuo to yield an oily residue containing 3-(1-ethoxycarbonyl-3-cyclohexylpropyl)amino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one. A mixture of this oil, potassium carbonate (4 g), tert-butyl chloroacetate (3 g), potassium iodide (0.2 g) and N,N-dimethylformamide (20 ml) is stirred overnight at room temperature, and then diluted with a mixture of water (300 ml) and ethyl acetate (200 ml). The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated in vacuo to yield an oil, which is purified by silica gel column chromatography using hexane-ethyl acetate (4:1) as an eluant to yield tert-butyl 3-(1-ethoxycarbonyl-3-cyclohexylpropyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (1 g) as a colorless oil.

Workup

  1. customAfter the absorption of hydrogen ceases
  2. customthe catalyst is removed by filtration
  3. customthe filtrate is evaporated in vacuo
  4. additionTo the residue are added water (50 ml) and ethyl acetate (200 ml)
  5. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
  6. customevaporated in vacuo
  7. customto yield an oily residue
  8. stirringis stirred overnight at room temperature
  9. customThe organic layer is separated
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customevaporated in vacuo
  12. customto yield an oil, which
  13. customis purified by silica gel column chromatography

Sources & evidence

ORD record
ord-62566be8ee384049bbcbfe0291b24a0f
Source dataset
uspto-grants-1986_05
Patent number
US04591458

Reaction notes

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