Acetic Acid Mixture with Hydrobromic Acid → (-)-cis-2-(4-methoxyphenyl)-3-propionyloxy-5-[2-(N-methylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

HRID 1381149Notes

Reaction equation

HRID 1381149 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@@H:15]([O:16][C:17](=[O:20])[CH2:18][CH3:19])[C:14](=[O:21])[N:13]([CH2:22][CH2:23][N:24](C(OCC3C=CC=CC=3)=O)[CH3:25])[C:12]3[CH:36]=[CH:37][C:38]([Cl:40])=[CH:39][C:11]=3[S:10]2)=[CH:5][CH:4]=1.Br.C(O)(=O)C>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@@H:15]([O:16][C:17](=[O:20])[CH2:18][CH3:19])[C:14](=[O:21])[N:13]([CH2:22][CH2:23][NH:24][CH3:25])[C:12]3[CH:36]=[CH:37][C:38]([Cl:40])=[CH:39][C:11]=3[S:10]2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 21893785Acetic Acid Mixture with Hydrobromic AcidHCID 70454921(-)-cis-2-(4-methoxyphenyl)-3-propionyloxy-5-[2-(N-benzyloxycarbonyl-N-methylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

Product 1

HCID 70454598(-)-cis-2-(4-methoxyphenyl)-3-propionyloxy-5-[2-(N-methylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-oneYield 87%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of 985 mg of (-)-cis-2-(4-methoxyphenyl)-3-propionyloxy-5-[2-(N-benzyloxycarbonyl-N-methylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, 1.6 ml of 25% hydrogen bromide-acetic acid and 5 ml of benzene is stirred for 5 hours under ice-cooling. Then, the mixture is evaporated at room temperature to remove benzene. Ether is added to the residue, and the precipitates are collected by filtration and washed with ether. Water is added to said precipitates, and the aqueous mixture is neutralized with potassium carbonate and extracted with ethyl acetate. The extract is washed with water, dried and evaporated under reduced pressure to remove solvent. 660 mg of (-)-cis-2-(4-methoxyphenyl)-3-propionyloxy-5-[2-(N-methylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one are obtained as caramel.

Workup

  1. temperaturecooling
  2. customThen, the mixture is evaporated at room temperature
  3. customto remove benzene
  4. additionEther is added to the residue
  5. filtrationthe precipitates are collected by filtration
  6. washwashed with ether
  7. additionWater is added
  8. customto said precipitates
  9. extractionextracted with ethyl acetate
  10. washThe extract is washed with water
  11. customdried
  12. customevaporated under reduced pressure
  13. customto remove solvent

Sources & evidence

ORD record
ord-4cbbbbc155144294b9aaeaf418186eb7
Source dataset
uspto-grants-1986_04
Patent number
US04585768

Reaction notes

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