Sodium Carbonate → (S)-5,11-Dihydro-5-[2-(1-[4-methoxyphenethyl]-2-pyrrolidinyl)ethyl]dibenzo[b,e][1,4]thiazepine

HRID 1460472Notes

Reaction equation

HRID 1460472 reaction equation
[H-].[K+].COC1C=CC(CCN2CCC[C@H]2[CH2:16][N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][S:20][C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]2=3)=CC=1.ClC[CH2:36][C@@H:37]1[CH2:41][CH2:40][CH2:39][N:38]1[CH2:42][CH2:43][C:44]1[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.ClCCl>[CH3:51][O:50][C:47]1[CH:46]=[CH:45][C:44]([CH2:43][CH2:42][N:38]2[CH2:39][CH2:40][CH2:41][C@H:37]2[CH2:36][CH2:16][N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][S:20][C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]2=3)=[CH:49][CH:48]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 82127Potassium hydrideHCID 9824029(S)-5,11-Dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]thiazepineHCID 54294922(S)-2-(2-chloroethyl)-1-(4-methoxyphenethyl)pyrrolidine

Product 1

HCID 54350689(S)-5,11-Dihydro-5-[2-(1-[4-methoxyphenethyl]-2-pyrrolidinyl)ethyl]dibenzo[b,e][1,4]thiazepineYield 78.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Potassium hydride (35% dispersion in oil, 110 mg) was added to a solution of 5,11-dihydrodibenzo[b,e][1,4]thiazepine (see Example 1) (570 mg) in DME (8 ml) and the mixture stirred at room temperature for 30 minutes, treated with a solution of (S)-2-(2-chloroethyl)-1-(4-methoxyphenethyl)pyrrolidine (480 mg) (prepared from the corresponding hydrochloride salt prepared in Preparation 4 by stirring a solution of the salt in dichloromethane with a slight excess of 10% aqueous sodium carbonate solution, separating the layers, drying the organic layer over sodium sulphate, and evaporating under reduced pressure to provide the desired free base) in DME (4 ml) and heated under reflux for two hours. The mixture was cooled to room temperature, quenched with water and extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, performing a gradient elution using initially dichloromethane/hexane (3:1) as eluant, changing to dichloromethane/methanol (97:3). The appropriate fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil, (460 mg, 58%).

Workup

  1. customprepared in Preparation 4
  2. customseparating the layers
  3. dry with materialdrying the organic layer over sodium sulphate
  4. customevaporating under reduced pressure
  5. customto provide the desired free base) in DME (4 ml)
  6. temperatureheated
  7. temperatureunder reflux for two hours
  8. temperatureThe mixture was cooled to room temperature
  9. customquenched with water
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with water
  12. dry with materialdried over sodium sulphate
  13. customevaporated under reduced pressure
  14. customThe residue was purified by chromatography on silica gel
  15. washa gradient elution
  16. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-49023e8a8d474062b753aca495199bf4
Source dataset
uspto-grants-1991_12
Patent number
US05071844

Reaction notes

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