Water → (R)-5-[1-(4-chlorophenethyl) pyrrolidine-3-yl]-5,11-dihydrodibenzo[b,e][1,4]oxazepine

HRID 1859466Notes

Reaction equation

HRID 1859466 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.[Cl:18][C:19]1[CH:36]=[CH:35][C:22]([CH2:23][CH2:24][N:25]2[CH2:29][CH2:28][C@H:27](OS(C)(=O)=O)[CH2:26]2)=[CH:21][CH:20]=1.O>CCCCCC.CS(C)=O>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][CH2:24][N:25]2[CH2:29][CH2:28][C@@H:27]([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)[CH2:26]2)=[CH:35][CH:36]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 110847985,11-Dihydrodibenzo[b,e][1,4]oxazepineHCID 86585525(S)-1-(4-chlorophenethyl)-3-methanesulfonyloxypyrrolidine

Product 1

HCID 12018624(R)-5-[1-(4-chlorophenethyl) pyrrolidine-3-yl]-5,11-dihydrodibenzo[b,e][1,4]oxazepine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolvent

Procedure

60% sodium hydride (34 mg, 0.87 mmol) was washed with hexane under argon atmosphere, and then suspended in dimethyl sulfoxide (4 ml). After stirring at room temperature for 25 minutes, 5,11-dihydrodibenzo[b,e][1,4]oxazepine (152 mg, 0.77 mmol) was added to the obtained suspension. They were stirred at room temperature for 25 minutes and then at 50° C. for 25 minutes. A solution of (S)-1-(4-chlorophenethyl)-3-methanesulfonyloxypyrrolidine (252 mg, 0.83 mmol) in dimethyl sulfoxide (2 ml) was added dropwise in the obtained solution, and they were stirred at 50° C. for 90 minutes. The reaction liquid was poured into water in ice cooling bath. 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 (2:1) and then with hexane and ethyl acetate (1:2) as the eluents. The appropriate fractions were combined, and the solvent was evaporated under reduced pressure to obtain (R)-5-[1-(4-chlorophenethyl) pyrrolidine-3-yl]-5,11-dihydrodibenzo[b,e][1,4]oxazepine in the form of a light yellow oil (44 mg, 14%).

Workup

  1. stirringThey were stirred at room temperature for 25 minutes
  2. waitat 50° C. for 25 minutes
  3. stirringwere stirred at 50° C. for 90 minutes
  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 (2:1)
  9. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-764192ac18bd4402b1935c0479f56d72
Source dataset
uspto-grants-2003_03
Patent number
US06528504B2

Reaction notes

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