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

HRID 1859458Notes

Reaction equation

HRID 1859458 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.CS(O[C@H:23]1[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[CH2:24]1)(=O)=O>CCCCCC.CS(C)=O>[CH3:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][CH2:29][CH2:28][N:25]2[CH2:26][CH2:27][C@@H:23]([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)[CH2:24]2)=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 110847985,11-Dihydrodibenzo[b,e][1,4]oxazepineHCID 57440107(s)-3-Methanesulfonyloxy-1-[3-(4-methoxyphenyl)propyl]pyrrolidine

Product 1

HCID 12148706(r)-5,11-Dihydro-5-[1-[3-(4-methoxyphenyl)propyl]pyrrolidine-3-yl]dibenzo[b,e][1,4]oxazepine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolvent

Procedure

60% sodium hydride (32 mg, 0.81 mmol) was washed with hexane under argon atmosphere, and then suspended in dimethyl sulfoxide (6 ml). After stirring at room temperature for 30 minutes, 5,11-dihydrodibenzo[b,e][1,4]oxazepine (142 g, 0.74 mmol) was added to the obtained suspension. They were stirred at room temperature for 40 minutes and then at 50° C. for 40 minutes. A solution of (S)-3-methanesulfonyloxy-1-[3-(4-methoxyphenyl)propyl]pyrrolidine (254 mg, 1.81 mmol) in dimethyl sulfoxide (3 ml) was added dropwise in the obtained solution, and they were stirred at 50° C. for 5 hours. The reaction liquid was poured into ice/water. After the extraction with a solvent mixture of hexane and ethyl acetate (1:1), 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 dichloromethane and then with a mixture of dichloromethane and methanol (50:1). The appropriate fractions were combined, and the solvent was evaporated under reduced pressure to obtain (R)-5,11-dihydro-5-[1-[3-(4-methoxyphenyl)propyl]pyrrolidine-3-yl]dibenzo[b,e][1,4]oxazepine in the form of a light yellow oil (78 mg, 25%).

Workup

  1. stirringThey were stirred at room temperature for 40 minutes
  2. waitat 50° C. for 40 minutes
  3. stirringwere stirred at 50° C. for 5 hours
  4. customThe reaction liquid
  5. extractionAfter the extraction
  6. additionwith a solvent mixture of hexane and ethyl acetate (1:1)
  7. customthe organic layer was dried
  8. customthe solvent was evaporated under reduced pressure
  9. washThe product was eluted with dichloromethane
  10. additionwith a mixture of dichloromethane and methanol (50:1)
  11. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-86a936d57abc4351af30d0706dba5780
Source dataset
uspto-grants-2003_03
Patent number
US06528504B2

Reaction notes

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