Benzylamine → 6-Benzyl-5,6,7,8-tetrahydro-4H-furo[2,3-d]azepine

HRID 611072Notes

Reaction equation

HRID 611072 reaction equation
O[CH2:2][CH2:3][C:4]1[CH:8]=[CH:7][O:6][C:5]=1[CH2:9][CH2:10]O.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.[CH2:26]([NH2:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C>ClCCl.O>[CH2:26]([N:33]1[CH2:2][CH2:3][C:4]2[CH:8]=[CH:7][O:6][C:5]=2[CH2:9][CH2:10]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 196002572,3-Di(2-hydroxyethyl)furan

Product 1

HCID 196001856-Benzyl-5,6,7,8-tetrahydro-4H-furo[2,3-d]azepine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1.208 g (7.735 mmol) of 2-[3-(2-hydroxyethyl)furan-2-yl]ethanol and 4.04 ml (23.2 mmol) of N,N-diisopropylethylamine in 50 ml of dichloromethane, 1.32 ml (17.0 mmol) of methanesulfonyl chloride was added dropwise under ice-cooling, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into water and extracted with diethyl ether 3 times. The combined organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting residue was dissolved in 100 ml of ethanol; 0.83 g (7.7 mmol) of benzylamine and 2.37 ml (17.0 mmol) of triethylamine were added, followed by stirring at 80° C. for 3 days. After the solvent was distilled off from the reaction mixture under reduced pressure, aqueous sodium hydroxide was added, followed by 3 extractions with ethyl acetate. The combined organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9/1) to yield the desired product.

Workup

  1. temperaturecooling
  2. extractionextracted with diethyl ether 3 times
  3. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. dissolutionThe resulting residue was dissolved in 100 ml of ethanol
  6. stirringby stirring at 80° C. for 3 days
  7. distillationAfter the solvent was distilled off from the reaction mixture under reduced pressure, aqueous sodium hydroxide
  8. additionwas added
  9. extractionfollowed by 3 extractions with ethyl acetate
  10. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  11. distillationthe solvent was distilled off under reduced pressure
  12. customThe resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-71084d9799164665a9dc8f55785f670f
Source dataset
uspto-grants-1999_12
Patent number
US05998433

Reaction notes

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