Potassium Iodide → tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

HRID 649414Notes

Reaction equation

HRID 649414 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH:21]([NH:27][C@@H:28]2[C:34](=[O:35])[NH:33][C:32]3[CH:36]=[CH:37][CH:38]=[CH:39][C:31]=3[S:30][CH2:29]2)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>O.CN(C)C=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([CH2:17][CH2:18][CH2:19][CH2:20][C@@H:21]([NH:27][C@@H:28]2[C:34](=[O:35])[N:33]([CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C:32]3[CH:36]=[CH:37][CH:38]=[CH:39][C:31]=3[S:30][CH2:29]2)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 66052tert-Butyl chloroacetateHCID 704162703(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]amino-2,3-dihydro-1,5(5H)-benzothiazepin-4-one

Product 1

HCID 54276750tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateYield 37.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]amino-2,3-dihydro-1,5(5H)-benzothiazepin-4-one (1.0 g), tert-butyl chloroacetate (0.27 g), potassium iodide (0.3 g), potassium carbonate (0.24 g) and N,N-dimethylformamide (10 ml) is stirred for 15 hours at room temperature. The mixture is poured into water (50 ml) and extracted with ethyl acetate (40 ml). The extract is washed with diluted hydrochloric acid, sodium bicarbonate solution and water successively, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give firstly tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (0.45 g) as a colorless oil.

Workup

  1. extractionextracted with ethyl acetate (40 ml)
  2. washThe extract is washed with diluted hydrochloric acid, sodium bicarbonate solution and water successively
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-1452556bc8b04489943170665b0ce3b0
Source dataset
uspto-grants-1988_04
Patent number
US04739066

Reaction notes

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