Ethyl bromoacetate → HCID 18625604, compound

HRID 1859471Notes

Reaction equation

HRID 1859471 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.Br[CH2:19][C:20]([O:22]CC)=[O:21].S([O-])(O)(=O)=O.[K+]>CCCCCC.CS(C)=O>[C:20]([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)([OH:22])=[O:21]

Participants

7

Reactant 4

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 110847985,11-Dihydrodibenzo[b,e][1,4]oxazepine

Product 1

HCID 18625604HCID 18625604, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolvent

Procedure

60% sodium hydride (3.60 g, 90 mmol) was washed with hexane under argon atmosphere, and then suspended in dimethyl sulfoxide (130 ml). 5,11-Dihydrodibenzo[b,e][1,4]oxazepine (14.8 g, 75.0 mmol) was added to the obtained suspension. They were stirred at room temperature for 60 minutes. A solution of ethyl bromoacetate (16.7 g, 150 mmol) in dimethyl sulfoxide (30 ml) was added dropwise in the obtained solution, and they were stirred at room temperature for 70 minutes and then at 50° C. for 2 hours. The reaction liquid was poured into 5% aqueous potassium hydrogensulfate solution. After the extraction with ethyl acetate, the organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution. After drying, the solvent was evaporated under reduced pressure. The obtained residue was dissolved in 200 ml of methanol. 200 ml of 4 M aqueous sodium hydroxide solution was added to the obtained solution, and they were stirred at room temperature for 1 hour. After the extraction with ethyl acetate, 40 ml of 6 M hydrochloric acid was added to the aqueous layer to adjust pH to 1. After the extraction with ethyl acetate, the organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution. After drying, the solvent was evaporated under reduced pressure. The obtained residue was subjected to silica gel column chromatography. The product was eluted with ethyl acetate and hexane (5:1) and then with ethyl acetate and hexane (1:3). The appropriate fractions were combined, and the solvent was evaporated under reduced pressure to obtain 5,11-dihydro-5-(carboxymethyl)dibenzo[b,e][1,4] oxazepine in the form of a light yellow solid (6.40 g, 33.5%).

Workup

  1. stirringwere stirred at room temperature for 70 minutes
  2. waitat 50° C. for 2 hours
  3. customThe reaction liquid
  4. extractionAfter the extraction with ethyl acetate
  5. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate solution
  6. customAfter drying
  7. customthe solvent was evaporated under reduced pressure
  8. dissolutionThe obtained residue was dissolved in 200 ml of methanol
  9. addition200 ml of 4 M aqueous sodium hydroxide solution was added to the obtained solution, and they
  10. stirringwere stirred at room temperature for 1 hour
  11. extractionAfter the extraction with ethyl acetate, 40 ml of 6 M hydrochloric acid
  12. additionwas added to the aqueous layer
  13. extractionAfter the extraction with ethyl acetate
  14. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate solution
  15. customAfter drying
  16. customthe solvent was evaporated under reduced pressure
  17. washThe product was eluted with ethyl acetate and hexane (5:1)
  18. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-daeb1fe4bd46490d9f84f30c98585084
Source dataset
uspto-grants-2003_03
Patent number
US06528504B2

Reaction notes

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