Chloroform → Deacetyldiltiazem

HRID 1285285Notes

Reaction equation

HRID 1285285 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][CH:20]=[CH:21][C:11]=3[S:10]2)=[CH:5][CH:4]=1.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].C(Cl)(Cl)Cl.Cl.[CH3:38][N:39]([CH3:43])[CH2:40][CH2:41]Cl>O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[C@@H:15]([OH:16])[C:14](=[O:17])[N:13]([CH2:41][CH2:40][N:39]([CH3:43])[CH3:38])[C:12]3[CH:18]=[CH:19][CH:20]=[CH:21][C:11]=3[S:10]2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 27336733-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-HCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 17749109Barium hydroxide, octahydrate

Product 1

HCID 91638DeacetyldiltiazemYield 97.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

3 g of cis-(+)-2-(4'-methoxyphenyl)-3-hydroxy-2,3-dihydro-1,5-benzothiazepine-4(5H)-one and 6.4 g of barium hydroxide octahydrate were added with vigorous stirring to 60 ml of chloroform and 10 ml of water. A solution of 3.2 g of 2-(dimethylamino)-ethyl chloride-hydrochloride in 5 ml of water was added dropwise to the above mixture in the course of 5 minutes. Stirring was continued for 24 hours at room temperature and then for 8 hours at 40°. After cooling to room temperature the aqueous phase was separated and discarded and the chloroform was removed under vacuum. Petroleum-ether (40°-60°) was added to the viscous residue which induced crystallisation. The precipitated crystals were filtered off and dried under vacuum to yield 3.63 g of cis-(+)-2-(4'-methoxyphenyl)-3-hydroxy-5-(2'-dimethylaminoethyl)-2,3-dihydro-1,5-benzothiazepine-4(5H)-one; m.p. 88°; [α]D22 +169 (C=0.25 CH 3 OH).

Workup

  1. waitfor 8 hours at 40°
  2. customwas separated
  3. customthe chloroform was removed under vacuum
  4. additionPetroleum-ether (40°-60°) was added to the viscous residue which
  5. customcrystallisation
  6. filtrationThe precipitated crystals were filtered off
  7. customdried under vacuum

Sources & evidence

ORD record
ord-75368457e20e499f92aad95fd435870d
Source dataset
uspto-grants-1986_01
Patent number
US04566995

Reaction notes

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