Triethylamine → tert-butyl 3(R)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

HRID 980626Notes

Reaction equation

HRID 980626 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[S:4][CH2:3]1.Br[CH:23]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:41](=[O:42])[C:40]2=[CH:43][CH:44]=[CH:45][CH:46]=[C:39]2[C:38]1=[O:47])[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[S:4][CH2:3]1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:38](=[O:47])[C:39]2=[CH:46][CH:45]=[CH:44][CH:43]=[C:40]2[C:41]1=[O:42])=[O:25])[CH3:28]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 13454543tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateHCID 13622535Ethyl 2-bromo-10-phthalimidodecanoate

Product 1

HCID 13622551tert-butyl 3(R)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

In 100 ml of acetonitrile are dissolved 1.7 g of tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate and 2.4 g of ethyl 2-bromo-10-phthalimidodecanoate, and 0.75 g of triethylamine is added to the solution. The mixture is heated at 80° C. for 3 days, concentrated under reduced pressure, diluted with 100 ml of water and extracted with 150 ml of ethyl acetate. The ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting oily substance is separated and purified by silicagel column chromatography (hexane:ethyl acetate=3:1 - 2:1) to give from the first fraction 0.9 g of tert-butyl 3(R)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate as a colorless oil.

Workup

  1. additionis added to the solution
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with 100 ml of water
  4. extractionextracted with 150 ml of ethyl acetate
  5. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting oily substance is separated
  8. custompurified by silicagel column chromatography (hexane:ethyl acetate=3:1 - 2:1)

Sources & evidence

ORD record
ord-e840da5615494ea5846045844c301d23
Source dataset
uspto-grants-1987_01
Patent number
US04638000

Reaction notes

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