Sodium hydride → (r)-(+)-5,11-Dihydro-5-[1-(4-fluorophenethyl)-2-pyrrolidinyl methyl]dibenzo[b,e][1,4]oxazepine

HRID 2304390Notes

Reaction equation

HRID 2304390 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]([F:33])=[CH:29][CH:28]=2)[CH2:20]1>CS(C)=O>[F:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][CH2:25][N:21]2[CH2:22][CH2:23][CH2:24][C@@H:20]2[CH2:19][N:8]2[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=3[CH2:12][O:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]2=3)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 110847985,11-Dihydrodibenzo[b,e][1,4]oxazepineHCID 15481944(S)-(+)-3-chloro-1-(4-fluorophenethyl)piperidine

Product 1

HCID 15481929(r)-(+)-5,11-Dihydro-5-[1-(4-fluorophenethyl)-2-pyrrolidinyl methyl]dibenzo[b,e][1,4]oxazepineYield 45.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Four-hundred milligrams (9.9 mmols) of 60% sodium hydride were washed with petroleum ether, and then suspended in 40 ml of dimethyl sulfoxide. To the suspension were added 1.5 g (7.6 mmols) of 5,11-dihydrodibenzo[b,e][1,4]oxazepine. The mixture was stirred in a nitrogen atmosphere at room temperature for 1 hour. To this reaction solution was added dropwise a solution of 2.2 g (9.1 mmols) of (S)-(+) -3-chloro-1-(4-fluorophenethyl)piperidine[[α]D25=+9.5° (c=1.0, ethano 1)] in 10 ml of dimethyl sulfoxide, and the mixed solution was stirred at room temperature for 4 days. The reaction solution was poured into ice water, 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 1:2. This mixed solvent was distilled off under reduced pressure to give 1.4 g of (R)-(+)-5,11-dihydro-5-[1-(4-fluorophenethyl)-2-pyrrolidinyl methyl]dibenzo[b,e][1,4]oxazepine as a pale yellow oil in a yield of 44%.

Workup

  1. stirringthe mixed solution was stirred at room temperature for 4 days
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water and with a saturated aqueous solution of sodium chloride in this order
  4. customdried
  5. distillationSubsequently, the solvent was distilled off under reduced pressure
  6. washeluted with a mixed solvent of ethyl acetate and hexane at a ratio of 1:2
  7. distillationThis mixed solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-3e319a39c78d45709400b67bfdd20ffa
Source dataset
uspto-grants-2002_08
Patent number
US06436922B1

Reaction notes

Loading…