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

HRID 649408Notes

Reaction equation

HRID 649408 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.C(#N)C.[CH2:25]([O:32][C:33]([N:35]1[CH2:40][CH2:39][CH:38]([CH2:41][CH2:42][CH2:43][CH2:44][CH:45](Cl)[C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:37][CH2:36]1)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[I-].[K+]>C(N(CC)CC)C>[CH2:25]([O:32][C:33]([N:35]1[CH2:36][CH2:37][CH:38]([CH2:41][CH2:42][CH2:43][CH2:44][C@@H:45]([NH:1][C@@H:2]2[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]3[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=3[S:4][CH2:3]2)[C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:39][CH2:40]1)=[O:34])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1.[CH2:25]([O:32][C:33]([N:35]1[CH2:36][CH2:37][CH:38]([CH2:41][CH2:42][CH2:43][CH2:44][C@H:45]([NH:1][C@@H:2]2[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]3[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=3[S:4][CH2:3]2)[C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:39][CH2:40]1)=[O:34])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 4875Potassium Iodide2×HCID 6342AcetonitrileHCID 13454543tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateHCID 19868892Ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate2×

Product 2

HCID 54276749tertbutyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(S)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateHCID 54276750tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (3.0 g), acetonitrile (100 ml), ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate (4.0 g), triethylamine (1.0 g) and potassium iodide (1.6 g) is stirred for 3 days at 80° C. Ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate (2.0 g) and potassium iodide (0.8 g) are added, and the stirring is continued for further 1 day at 80° C. The mixture is concentrated in vacuo, diluted with water (100 ml) and extracted with ethyl acetate (300 ml). The extract is washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. Purification of the residual oil by silicagel column chromatography (hexane:ethyl acetate=2:1) gives 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 (3.1 g) as a colorless oil and tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1 (S)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (2.1 g) as a colorless oil.

Workup

  1. waitthe stirring is continued for further 1 day at 80° C
  2. concentrationThe mixture is concentrated in vacuo
  3. additiondiluted with water (100 ml)
  4. extractionextracted with ethyl acetate (300 ml)
  5. washThe extract is washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated in vacuo
  8. customPurification of the residual oil by silicagel column chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-abfa6d969662415fa9094940353603d2
Source dataset
uspto-grants-1988_04
Patent number
US04739066

Reaction notes

Loading…