Triethylamine → 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]amino-2,3-dihydro-1,5(5H)-benzothiazepin-4-one

HRID 649424Notes

Reaction equation

HRID 649424 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10][CH2:11][C@H:12]([NH:16][CH:17]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:18][CH2:19][CH2:20][CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[CH2:24][CH2:23]1)[C:13](O)=[O:14].P(C#N)(=O)(OCC)OCC.C(N(CC)CC)C>CN(C)C=O.O>[CH2:31]([O:30][C:28]([N:25]1[CH2:24][CH2:23][CH:22]([CH2:21][CH2:20][CH2:19][CH2:18][CH:17]([NH:16][C@@H:12]2[C:13](=[O:14])[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[S:10][CH2:11]2)[C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:27][CH2:26]1)=[O:29])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 704163783-(o-aminophenyl)thio-2(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]aminopropionic acid dihydrochloride

Product 1

HCID 704162703(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]amino-2,3-dihydro-1,5(5H)-benzothiazepin-4-oneYield 65.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In N,N-dimethylformamide (5 ml) is dissolved 3-(o-aminophenyl)thio-2(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]aminopropionic acid dihydrochloride (0.16 g), and diethyl phosphorocyanidate (0.3 ml) is added dropwise to the solution. To the mixture is added triethylamine (0.2 ml) and the reaction mixture is stirred under ice-cooling for 1 hour. The reaction mixture is diluted with water (100 ml) and extracted with ethyl acetate (50 ml). The extract is washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by silicagel column chromatography (hexane:acetone=2:1) to give 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]amino-2,3-dihydro-1,5(5H)-benzothiazepin-4-one (0.09 g) as a colorless oil.

Workup

  1. additionis added dropwise to the solution
  2. temperaturecooling for 1 hour
  3. extractionextracted with ethyl acetate (50 ml)
  4. washThe extract is washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by silicagel column chromatography (hexane:acetone=2:1)

Sources & evidence

ORD record
ord-fc2f96549fea47829d2419fba595b7aa
Source dataset
uspto-grants-1988_04
Patent number
US04739066

Reaction notes

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