Sodium hydride → (R)-2-fluoro-5,11-dihydro-5-[1-(4-pyrrolidinophenethyl)pyrrolidin-2-ylmethyl]dibenzo[b,e][1,4]oxazepine

HRID 2251889Notes

Reaction equation

HRID 2251889 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:18]=[CH:17][C:7]2[NH:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[O:11][CH2:12][C:6]=2[CH:5]=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]([N:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)=[CH:30][CH:29]=2)[CH2:21]1.C(=O)([O-])O.[Na+]>CCCCCC.CS(C)=O.C(OCC)(=O)C>[F:3][C:4]1[CH:18]=[CH:17][C:7]2[N:8]([CH2:24][C@H:23]3[CH2:25][CH2:20][CH2:21][N:22]3[CH2:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([N:34]4[CH2:35][CH2:36][CH2:37][CH2:38]4)=[CH:32][CH:33]=3)[C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[O:11][CH2:12][C:6]=2[CH:5]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 110747792-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepineHCID 69201531(R)-3-chloro-1-(4-pyrrolidinophenethyl)piperidine

Product 1

HCID 59644017(R)-2-fluoro-5,11-dihydro-5-[1-(4-pyrrolidinophenethyl)pyrrolidin-2-ylmethyl]dibenzo[b,e][1,4]oxazepine

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

60% sodium hydride (348 mg, 8.7 mmol) was washed with hexane in argon stream and then suspended in dimethyl sulfoxide (50 ml), and the obtained suspension was stirred at room temperature for 30 minutes. 2-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepine (1.70 g, 7.90 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-pyrrolidinophenethyl)piperidine (2.64 g, 9.02 mmol) in dimethyl sulfoxide (25 ml) was added dropwise to the obtained solution, and they were stirred at 50° C. for 3 hours. The reaction mixture was distributed into saturated aqueous sodium hydrogencarbonate 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 (6:1) and then 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)-2-fluoro-5,11-dihydro-5-[1-(4-pyrrolidinophenethyl)pyrrolidin-2-ylmethyl]dibenzo[b,e][1,4]oxazepine in the form of a light yellow oily substance (2.29 g, 68%).

Workup

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

Sources & evidence

ORD record
ord-c2f03d51cc5b4253b622649679266803
Source dataset
uspto-grants-2008_01
Patent number
US07320973B2

Reaction notes

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