Dichloromethane → Deacetyldiltiazem

HRID 1285284Notes

Reaction equation

HRID 1285284 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.[CH3:37][N:38]([CH3:42])[CH2:39][CH2:40]Cl>[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.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]([CH2:40][CH2:39][N:38]([CH3:42])[CH3:37])[C:12]3[CH:18]=[CH:19][CH:20]=[CH:21][C:11]=3[S:10]2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 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 99.8%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent2×

Procedure

0.2 g of triethylbenzylammonium chloride, 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 under vigorous stirring to 60 ml of methylene chloride 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 during 5 minutes. Stirring was continued at room temperature for 1 hour and then at 40° for 24 hours. After cooling to room temperature the aqueous phase was separated and discarded and the methylene chloride was removed under vacuum. (Petroleum ether (40°-60°) was added to the viscous residue with induced crystallisation. The crystals obtained were filtered off and dried under vacuum to yield 3.7 g of cis-(+)-2-(4'-methoxyphenyl)-3-hydroxy-5-(2'-dimethylaminoethyl)-2,3-dihydro-1,5-benzothiazepine-4(5H)-one; m.p.88°-90°; [α]D27 +169 (C=0.25, CH3OH).

Workup

  1. waitat 40° for 24 hours
  2. customwas separated
  3. customthe methylene chloride was removed under vacuum
  4. addition(Petroleum ether (40°-60°) was added to the viscous residue with induced crystallisation
  5. customThe crystals obtained
  6. filtrationwere filtered off
  7. customdried under vacuum

Sources & evidence

ORD record
ord-706af7535b024208801c7420ea60cd25
Source dataset
uspto-grants-1986_01
Patent number
US04566995

Reaction notes

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