Sodium Chloride → (R)-3-fluoro-5,11-dihydro-5-[1-(4-methoxyphenethyl)piperidine-2-ylmethyl]dibenzo[b,e][1,4]oxazepine

HRID 2251876Notes

Reaction equation

HRID 2251876 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]2[CH2:13][O:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[NH:9][C:8]=2[CH:18]=1.Cl[C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH2:21]1.[Cl-].[Na+].[CH3:38]CCCCC>CS(C)=O.C(OCC)(=O)C>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[CH2:13][O:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[N:9]([CH2:38][C@H:23]3[CH2:24][CH2:25][CH2:20][CH2:21][N:22]3[CH2:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[C:8]=2[CH:18]=1

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 8058HexaneHCID 24758Sodium hydrideHCID 15481943(R)-3-chloro-1-(4-methoxyphenethyl)piperidineHCID 692001863-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepine

Product 1

HCID 69198718(R)-3-fluoro-5,11-dihydro-5-[1-(4-methoxyphenethyl)piperidine-2-ylmethyl]dibenzo[b,e][1,4]oxazepine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

60% sodium hydride (44 mg, 1.1 mmol) was washed with hexane in argon stream and then suspended in dimethyl sulfoxide (5 ml), and the obtained suspension was stirred at room temperature for 30 minutes. 3-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepine (0.22 g, 1.0 mmol) was added to the suspension, and they were stirred at room temperature for 30 minutes and then at 50° C. for additional 30 minutes. A solution of (R)-3-chloro-1-(4-methoxyphenethyl)piperidine (0.25 g, 1.0 mmol, prepared by a method disclosed in International Patent No. 9733885A1) in dimethyl sulfoxide (2 ml) was added dropwise to the obtained solution, and they were stirred at 50° C. for 6 hours. The reaction mixture was distributed into saturated aqueous sodium chloride solution and ethyl acetate. The organic layer was dried and the solvent was evaporated under reduced pressure. The residue was subjected to the silica gel column chromatography. After the elution with hexane and ethyl acetate (7:3) as the eluent, suitable fractions were collected and the solvent was evaporated under reduced pressure to obtain (R)-3-fluoro-5,11-dihydro-5-[1-(4-methoxyphenethyl)piperidine-2-ylmethyl]dibenzo[b,e][1,4]oxazepine in the form of a light yellow oily substance (0.30 g, 70%).

Workup

  1. stirringwere stirred at room temperature for 30 minutes
  2. waitat 50° C. for additional 30 minutes
  3. stirringwere stirred at 50° C. for 6 hours
  4. customThe organic layer was dried
  5. customthe solvent was evaporated under reduced pressure
  6. washAfter the elution with hexane and ethyl acetate (7:3) as the eluent, suitable fractions
  7. customwere collected
  8. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-f88b693f5b83456180f47a9591687ae4
Source dataset
uspto-grants-2008_01
Patent number
US07320973B2

Reaction notes

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