Triethylamine → tert-butyl 3(S)-[1(R)-ethoxycarbonyl-7-phthalimidoheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

HRID 280938Notes

Reaction equation

HRID 280938 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[O:4][CH2:3]1.Br[CH:23]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][N:35]1[C:39](=[O:40])[C:38]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:37]2[C:36]1=[O:45])[C:24]([O:26][CH2:27][CH3:28])=[O:25].C(N(CC)CC)C>C(#N)C>[CH2:27]([O:26][C:24]([C@H:23]([NH:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[O:4][CH2:3]1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][N:35]1[C:36](=[O:45])[C:37]2=[CH:44][CH:43]=[CH:42][CH:41]=[C:38]2[C:39]1=[O:40])=[O:25])[CH3:28]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 13622530tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetateHCID 13622533Ethyl 2-bromo-8-phthalimidooctanoate

Product 1

HCID 13622563tert-butyl 3(S)-[1(R)-ethoxycarbonyl-7-phthalimidoheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetateYield 25.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

In 100 ml of acetonitrile are dissolved 2.8 g of tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate and 7.6 g of ethyl 2-bromo-8-phthalimidooctanoate, and 1.3 g of triethylamine is added to the solution. After heating at 80° C. for 3 days, the reaction solution is concentrated under reduced pressure, diluted with 200 ml of water and extracted with 200 ml of ethyl acetate. The ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Ethyl acetate (10 ml) and oxalic acid (2.8 g) are added to the residue, and 200 ml of petroleum ether is added to the solution. After shaking, the resulting solution is allowed to stand. The supernatant is removed by decantation and 150 ml of water and 200 ml of ethyl acetate are added to the precipitate. The mixture is neutralized with sodium bicarbonate and the ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The oily product is separated and purified by silica gel column chromatography to give 1.5 g of tert-butyl 3(S)-[1(R)-ethoxycarbonyl-7-phthalimidoheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate from the first fraction.

Workup

  1. additionis added to the solution
  2. concentrationthe reaction solution is concentrated under reduced pressure
  3. additiondiluted with 200 ml of water
  4. extractionextracted with 200 ml of ethyl acetate
  5. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionEthyl acetate (10 ml) and oxalic acid (2.8 g) are added to the residue, and 200 ml of petroleum ether
  8. additionis added to the solution
  9. customThe supernatant is removed by decantation and 150 ml of water and 200 ml of ethyl acetate
  10. additionare added to the precipitate
  11. dry with materialthe ethyl acetate layer is dried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe oily product is separated
  14. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-11be872e1bae4b8285938881dc9323ca
Source dataset
uspto-grants-1986_05
Patent number
US04591458

Reaction notes

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