Sodium hydride → (r)-5,11-Dihydro-5-[1-(4-dimethylaminophenethyl)pyrrolidine-3-yl]dibenzo[b,e][1,4]oxazepine

HRID 1859453Notes

Reaction equation

HRID 1859453 reaction equation
[H-].[Na+].[CH:3]1[C:13]2[CH2:12][O: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.[CH3:18][N:19]([CH3:38])[C:20]1[CH:37]=[CH:36][C:23]([CH2:24][CH2:25][N:26]2[CH2:30][CH2:29][C@H:28](OS(C)(=O)=O)[CH2:27]2)=[CH:22][CH:21]=1>CCCCCC.CS(C)=O>[CH3:38][N:19]([CH3:18])[C:20]1[CH:21]=[CH:22][C:23]([CH2:24][CH2:25][N:26]2[CH2:30][CH2:29][C@@H:28]([N:8]3[C:7]4[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=4[CH2:12][O:11][C:10]4[CH:14]=[CH:15][CH:16]=[CH:17][C:9]3=4)[CH2:27]2)=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 110847985,11-Dihydrodibenzo[b,e][1,4]oxazepineHCID 86585524(S)-1-(4-dimethylaminophenethyl)-3-methanesulfonyloxy-pyrrolidine

Product 1

HCID 12018622(r)-5,11-Dihydro-5-[1-(4-dimethylaminophenethyl)pyrrolidine-3-yl]dibenzo[b,e][1,4]oxazepine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolvent

Procedure

60% sodium hydride (160 mg, 4.0 mmol) was washed with hexane under argon atmosphere, and then suspended in dimethyl sulfoxide (12 ml). After stirring at room temperature for 30 minutes, 5,11-dihydrodibenzo[b,e][1,4]oxazepine (790 g, 4.0 mmol) was added to the obtained suspension. They were stirred at room temperature for 60 minutes and then at 50° C. for 60 minutes. A solution of (S)-1-(4-dimethylaminophenethyl)-3-methanesulfonyloxypyrrolidine (378 mg, 1.21 mmol) in dimethyl sulfoxide (7 ml) was added dropwise in the obtained solution, and they were stirred at 50° C. for 3 hours. The reaction liquid was poured into ice/water. After the extraction with ethyl acetate, the organic layer was dried and the solvent was evaporated under reduced pressure. The obtained residue was subjected to silica gel column chromatography. The product was eluted with hexane and ethyl acetate (10:1), then with hexane and ethyl acetate (3:1) and finally with a mixture of the same solvents (1:1). The appropriate fractions were combined, and the solvent was evaporated under reduced pressure to obtain (R)-5,11-dihydro-5-[1-(4-dimethylaminophenethyl)pyrrolidine-3-yl]dibenzo[b,e][1,4]oxazepine in the form of a light yellow oil (196 mg, 39%).

Workup

  1. stirringThey were stirred at room temperature for 60 minutes
  2. waitat 50° C. for 60 minutes
  3. stirringwere stirred at 50° C. for 3 hours
  4. customThe reaction liquid
  5. extractionAfter the extraction with ethyl acetate
  6. customthe organic layer was dried
  7. customthe solvent was evaporated under reduced pressure
  8. washThe product was eluted with hexane and ethyl acetate (10:1)
  9. additionwith hexane and ethyl acetate (3:1) and finally with a mixture of the same solvents (1:1)
  10. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6775aff3255b49509cda06eaa18e1d3f
Source dataset
uspto-grants-2003_03
Patent number
US06528504B2

Reaction notes

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