Sodium Chloride → (R)-3-fluoro-5,11-dihydro-5-[1-(3-pyrrolidinophenethyl)pyrrolidin-3-yl]dibenzo[b,e]-[1,4]oxazepine

HRID 2251899Notes

Reaction equation

HRID 2251899 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.CS(O[C@H:24]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([N:37]3[CH2:41][CH2:40][CH2:39][CH2:38]3)[CH:32]=2)[CH2:25]1)(=O)=O.[Cl-].[Na+]>CCCCCC.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]([C@@H:28]3[CH2:24][CH2:25][N:26]([CH2:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([N:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)[CH:32]=4)[CH2:27]3)[C:8]=2[CH:18]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 692001863-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepineHCID 86592731(S)-3-methanesulfonyloxy-1-(3-pyrrolidinophenethyl)pyrrolidine

Product 1

HCID 12990602(R)-3-fluoro-5,11-dihydro-5-[1-(3-pyrrolidinophenethyl)pyrrolidin-3-yl]dibenzo[b,e]-[1,4]oxazepine

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

60% sodium hydride (88 mg, 2.2 mmol) was washed with hexane in argon gas stream and then suspended in dimethyl sulfoxide (10 ml). The obtained suspension was stirred at room temperature for 30 minutes. 3-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepine (0.43 g, 2.0 mmol) was added to the suspension, and they were stirred at room temperature for 30 minutes. After stirring at 50° C. for 30 minutes, a solution of (S)-3-methanesulfonyloxy-1-(3-pyrrolidinophenethyl)pyrrolidine (0.34 g, 1.0 mmol) in dimethyl sulfoxide (4 ml) was added dropwise to the obtained solution, and they were stirred at 70° C. for 2 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 (1:1) 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-(3-pyrrolidinophenethyl)pyrrolidin-3-yl]dibenzo[b,e]-[1,4]oxazepine in the form of a light yellow oily substance (0.19 g, 42%).

Workup

  1. stirringwere stirred at room temperature for 30 minutes
  2. stirringAfter stirring at 50° C. for 30 minutes
  3. stirringwere stirred at 70° C. for 2 hours
  4. customThe organic layer was dried
  5. customthe solvent was evaporated under reduced pressure
  6. washAfter the elution with hexane and ethyl acetate (1:1) as the eluent, suitable fractions
  7. customwere collected
  8. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-d87cb35421ca4d648a2e37af19f5a60a
Source dataset
uspto-grants-2008_01
Patent number
US07320973B2

Reaction notes

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