Methyl iodide → 1-Benzhydryl-3-methoxy-3-methylazetidine

HRID 1418656Notes

Reaction equation

HRID 1418656 reaction equation
Cl.[CH3:2][C:3]1(O)[CH2:6][NH:5][CH2:4]1.[H-].[Na+].I[CH3:11].[CH3:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].[C:18]([O:21][CH2:22][CH3:23])(=O)C.O1[CH2:28][CH2:27][CH2:26][CH2:25]1>>[C:14]1([CH:6]([C:3]2[CH:2]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:5]2[CH2:4][C:22]([O:21][CH3:18])([CH3:23])[CH2:11]2)[CH:13]=[CH:12][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 5

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 115427813-methylazetidin-3-ol HydrochlorideHCID 21226206Ethyl acetate hexane

Product 1

HCID 152086291-Benzhydryl-3-methoxy-3-methylazetidineYield 50%

Procedure

A slurry of 1-diphenylmethyl)-3-methyl-3-azetidinol hydrochloride (5.00 g, 17.2 mmol) in dry tetrahydrofuran (200 mL) was cooled with an ice bath to 0° C. and treated with sodium hydride (2.10 g of a 60% dispersion in oil, 51.8 mmol) under nitrogen. The cooling bath was removed and the mixture warmed to reflux temperature for 15 min. After cooling to room temperature, iodomethane (7.40 g, 3.22 mL, 51.8 mmol) was added. When the addition was completed, the reaction mixture was heated to reflux temperature for 15 hours. TLC analysis (9:1 hexane/ethyl acetate) revealed the methylation to be complete. The reaction mixture was quenched with saturated aqueous ammonium chloride. The mixture was transferred to a separatory funnel with ethyl acetate and water and then extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was chromatographed over silica gel, eluting with 9:1 ethyl acetate/hexane. Concentration of appropriate fractions afforded 2.30 g (50%) of the title compound as a colorless oil with MS(EI) 267 (M+).

Workup

  1. customThe cooling bath was removed
  2. temperaturethe mixture warmed
  3. temperatureto reflux temperature for 15 min
  4. additionWhen the addition
  5. temperaturethe reaction mixture was heated
  6. temperatureto reflux temperature for 15 hours
  7. customThe reaction mixture was quenched with saturated aqueous ammonium chloride
  8. customThe mixture was transferred to a separatory funnel with ethyl acetate and water
  9. extractionextracted with ethyl acetate
  10. washThe combined organic extracts were washed with water and brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe crude product was chromatographed over silica gel
  15. washeluting with 9:1 ethyl acetate/hexane

Sources & evidence

ORD record
ord-2e8fa9fdceaa4d4e89481d9069a56b30
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

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