Potassium Hydroxide → (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(N-benzyloxycarbonyl-N-methylamino)ethyl]-8-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

HRID 1981935Notes

Reaction equation

HRID 1981935 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@@H:15]([OH:16])[C:14](=[O:17])[NH:13][C:12]3[CH:18]=[CH:19][C:20]([CH3:22])=[CH:21][C:11]=3[S:10]2)=[CH:5][CH:4]=1.[OH-].[K+].[CH2:25]([O:32][C:33]([N:35]([CH2:37][CH2:38]Cl)[CH3:36])=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CS(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@@H:15]([OH:16])[C:14](=[O:17])[N:13]([CH2:38][CH2:37][N:35]([C:33]([O:32][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:34])[CH3:36])[C:12]3[CH:18]=[CH:19][C:20]([CH3:22])=[CH:21][C:11]=3[S:10]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 10358332HCID 10358332, compoundHCID 13592063Benzyl (2-chloroethyl)methylcarbamate

Product 1

HCID 70467950(+)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(N-benzyloxycarbonyl-N-methylamino)ethyl]-8-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-oneYield 91.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 2 g of (±)-cis-2-(4-methoxyphenyl)-3-hydroxy- 8-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, 0.42 g of powdered potassium hydroxide and 15 ml of dimethylsulfoxide is stirred at 50° C. for 30 minutes. A solution of 2.64 g of 2-(N-benzyloxycarbonyl-N-methylamino)ethyl chloride in 5 ml of dimethylsulfoxide is added to the mixture, and the mixture is stirred at 50° C. for 3 days. The mixture is poured into ice-water, and the aqueous mixture is extracted with ethyl acetate. The extract is washed with a saturated sodium chloride solution, dried and evaporated under reduced pressure to remove solvent. The residue is purified by silica gel chromatography (solvent, chloroform: ethyl acetate=10:1). 2.95 g of (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(N-benzyloxycarbonyl-N-methylamino)ethyl]-8-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one are obtained as an oil.

Workup

  1. stirringthe mixture is stirred at 50° C. for 3 days
  2. extractionthe aqueous mixture is extracted with ethyl acetate
  3. washThe extract is washed with a saturated sodium chloride solution
  4. customdried
  5. customevaporated under reduced pressure
  6. customto remove solvent
  7. customThe residue is purified by silica gel chromatography (solvent, chloroform: ethyl acetate=10:1)

Sources & evidence

ORD record
ord-714051114a62466294d80a2bba860537
Source dataset
uspto-grants-1986_06
Patent number
US04594342

Reaction notes

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