Sodium hydride → (r)-(+)-5,11-Dihydro-5-[1-(3,4-dimethoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine

HRID 365317Notes

Reaction equation

HRID 365317 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[C@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=2)[CH2:20]1>CS(C)=O>[CH3:36][O:35][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][C:30]=1[O:33][CH3:34])[CH2:26][CH2:25][N:21]1[CH2:22][CH2:23][CH2:24][C@@H:20]1[CH2:19][N:8]1[C:7]2[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=2[CH2:12][O:11][C:10]2[CH:14]=[CH:15][CH:16]=[CH:17][C:9]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 110847985,11-Dihydrodibenzo[b,e][1,4]oxazepineHCID 15481946(S)-(+)-3-chloro-1-(3,4-dimethoxyphenethyl)piperidine

Product 1

HCID 15481931(r)-(+)-5,11-Dihydro-5-[1-(3,4-dimethoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepineYield 85%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Sixty-percent sodium hydride (470 mg, 12 mmols) was washed with petroleum ether, and then suspended in 50 ml of dimethyl sulfoxide. To the suspension were added 1.5 g (7.5 mmols) of 5,11-dihydrodibenzo[b,e][1,4]oxazepine. The mixture was stirred in a nitrogen atmosphere at room temperature for 30 minutes. To this reaction solution was added dropwise a solution of 3.2 g (11 mmols) of (S)-(+)-3-chloro-1-(3,4-dimethoxyphenethyl)piperidine [[α]D25 =+20.3° (c=0.9, ethano l)] in 30 ml of dimethyl sulfoxide, and the mixed solution was stirred at 50° C. for 5 hours. The reaction solution was poured into ice wate r, and extracted with ethyl acetate. The organic layer was washed with water and with a saturated aqueous solution of sodium chloride in this order, and dried. Subsequently, the solvent was distilled off under reduced pressure. The resulting residue was subjected to column chromatography, and eluted with a mixed solvent of ethyl acetate and hexane at a ratio of 1:3. This mixed solvent was distilled off under reduced pressure. Further, the thus-obtained residue was subjected to column chromatography, and eluted with a mixed solvent of chloroform and methanol at a ratio of 300:1. The mixed solvent was then distilled off under reduced pressure to give 2.8 g of (R)-(+)-5,11-dihydro-5-[1-(3,4-dimethoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine as a pale yellow oil in a yield of 85%.

Workup

  1. stirringthe mixed solution was stirred at 50° C. for 5 hours
  2. additionThe reaction solution was poured into ice wate r
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water and with a saturated aqueous solution of sodium chloride in this order
  5. customdried
  6. distillationSubsequently, the solvent was distilled off under reduced pressure
  7. washeluted with a mixed solvent of ethyl acetate and hexane at a ratio of 1:3
  8. distillationThis mixed solvent was distilled off under reduced pressure
  9. washeluted with a mixed solvent of chloroform and methanol at a ratio of 300:1
  10. distillationThe mixed solvent was then distilled off under reduced pressure

Sources & evidence

ORD record
ord-770930b30fff4fd0bc1530f652b33217
Source dataset
uspto-grants-2000_10
Patent number
US06127361

Reaction notes

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