Potassium hydride → (S)-5,11-Dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]thiazepine

HRID 1460471Notes

Reaction equation

HRID 1460471 reaction equation
[H-].[K+].[CH:3]1[C:13]2[CH2:12][S:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.Cl[C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH2:20]1>COCCOC>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][CH2:25][N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:8]2[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=3[CH2:12][S:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]2=3)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 82127Potassium hydrideHCID 8269716,11-Dihydrobenzo[c][1,5]benzothiazepineHCID 15481943(R)-3-chloro-1-(4-methoxyphenethyl)piperidine

Product 1

HCID 9824029(S)-5,11-Dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]thiazepineYield 12%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Potassium hydride (35% dispersion in oil, 229 mg) was added to a solution of 5,11-dihydrodibenzo[b,e][1,4]thiazepine (see U.S. Pat. No. 3,188,322 [Chem. Abs., 63, 8384h (1965)] and I. Udea and S. Umio, Bull. Chem. Soc. Japan, 48(8), 2323 (1975)) (425 mg) in DME (1,2-dimethoxyethane) (20 ml) and the mixture stirred at room temperature for 30 minutes, treated with a solution of (R)-3-chloro-1-(4-methoxyphenethyl)piperidine (see Preparation 1) (507 mg) in DME (5 ml) and heated under reflux for 18 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 as eluant and changing to dichloromethane/saturated methanolic ammonia (98:2). The appropriate fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil, (100 mg, 12%), [α]58925 -60.9° (c=0.57 in ethanol).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 18 hours
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulphate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel
  9. washa gradient elution
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-d8c8e1756bf44859a3ed78fecb995213
Source dataset
uspto-grants-1991_12
Patent number
US05071844

Reaction notes

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