Hydrochloric Acid → 1-(Diphenylmethyl)azetidin-3-one

HRID 253054Notes

Reaction equation

HRID 253054 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]([N:24]1[CH2:27][CH:26]([OH:28])[CH2:25]1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl>C(Cl)Cl.C(N(CC)CC)C>[CH:11]([N:24]1[CH2:27][C:26](=[O:28])[CH2:25]1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 3304481-(Diphenylmethyl)azetidin-3-ol

Product 1

HCID 37355581-(Diphenylmethyl)azetidin-3-oneYield 92.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

A solution of oxalyl chloride (1.92 mL) in methylene chloride (70 mL) was cooled to −74° C. under nitrogen-gas atmosphere and thereto was added dropwise dimethylsulfoxide (3.22 mL) over a period of 15 minutes. The mixture was stirred at the same temperature for 20 minutes and thereto was added dropwise a solution of 1-benzhydryl-3-hydroxyazetidine (5 g) in methylene chloride (25 mL) over a period of 45 minutes. The mixture was stirred at the same temperature for 75 minutes. Thereto was added dropwise triethylamine (11.6 mL) over a period of 20 minutes and the mixture was stirred at the same temperature for 150 minutes. The reaction mixture was warmed to 0° C. and thereto was added dropwise an aqueous 1N HCl solution (64 mL). The mixture was stirred at room temperature and the aqueous layer was separated. To the organic layer was added an aqueous 1N HCl solution. The mixture was stirred and the aqueous layer was separated (said extraction procedure was repeated three times). The combined aqueous layer was neutralized (pH 9) with an aqueous 2N sodium hydroxide solution under stirring and extracted with ethyl acetate. The extract was washed with a brine, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the resultant crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate=100/0 to 90/10) to obtain 1-benzhydrylazetidin-3-one (4.57 g, Yield: 92%) as a white solid.

Workup

  1. stirringThe mixture was stirred at the same temperature for 75 minutes
  2. stirringthe mixture was stirred at the same temperature for 150 minutes
  3. stirringThe mixture was stirred at room temperature
  4. customthe aqueous layer was separated
  5. additionTo the organic layer was added an aqueous 1N HCl solution
  6. stirringThe mixture was stirred
  7. customthe aqueous layer was separated
  8. extraction(said extraction procedure was repeated three times)
  9. stirringunder stirring
  10. extractionextracted with ethyl acetate
  11. washThe extract was washed with a brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationThe filtrate was concentrated in vacuo
  15. customthe resultant crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate=100/0 to 90/10)

Sources & evidence

ORD record
ord-57aabbc0d06b4985bd60eb72a16805e9
Source dataset
uspto-grants-2011_01
Patent number
US07872006B2

Reaction notes

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