Acetonitrile → tert-butyl 3(S)-[1(R)ethoxycarbonyl-6-phthalimidohexyl]-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

HRID 280944Notes

Reaction equation

HRID 280944 reaction equation
N[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][N:34]1[C:38](=[O:39])[C:37]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:36]2[C:35]1=[O:44])[C:24]([O:26][CH2:27][CH3:28])=[O:25].C(#[N:47])C>C(N(CC)CC)C>[CH2:27]([O:26][C:24]([C@@H:23]([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][CH:3]1[NH2:47])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][N:34]1[C:38](=[O:39])[C:37]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:36]2[C:35]1=[O:44])=[O:25])[CH3:28]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 13622530tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetateHCID 13622532Ethyl 2-bromo-7-phthalimidoheptanoate

Product 1

HCID 70455253tert-butyl 3(S)-[1(R)ethoxycarbonyl-6-phthalimidohexyl]-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (2 g), ethyl 2-bromo-7-phthalimidoheptanoate (3.9 g), acetonitrile (100 ml) and triethylamine (0.9 g) is heated at 80° C. for 3 days. After evaporation of acetonitrile, water (150 ml) and ethyl acetate (200 ml) is added to the residue, and the mixture is agitated thoroughly. The ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue is dissolved in a mixture of ethyl acetate (10 ml) and oxalic acid (2 g). The resulting solution is diluted with petroleum ether (200 ml) and agitated thoroughly. The supernatant layer is removed by decantation. To the precipitate are added water (150 ml), ethyl acetate (200 ml) and sodium bicarbonate with stirring. The ethyl acetate layer is separated, dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue is chromatographed graphed on silica gel using hexane-ethyl acetate (2:1-1:1) as an eluent. Evaporation of the first fraction affords tert-butyl 3(S)-[1(R)ethoxycarbonyl-6-phthalimidohexyl]-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.65 g) as a colorless oil.

Workup

  1. customAfter evaporation of acetonitrile, water (150 ml) and ethyl acetate (200 ml)
  2. additionis added to the residue
  3. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe oily residue is dissolved in a mixture of ethyl acetate (10 ml) and oxalic acid (2 g)
  6. additionThe resulting solution is diluted with petroleum ether (200 ml)
  7. stirringagitated thoroughly
  8. customThe supernatant layer is removed by decantation
  9. additionTo the precipitate are added water (150 ml), ethyl acetate (200 ml) and sodium bicarbonate
  10. stirringwith stirring
  11. customThe ethyl acetate layer is separated
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe oily residue is chromatographed
  15. customEvaporation of the first fraction

Sources & evidence

ORD record
ord-4112e7dbb336411a99a739ac8ef81b16
Source dataset
uspto-grants-1986_05
Patent number
US04591458

Reaction notes

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