Methyl iodide → 1-Benzhydryl-3-(2-methoxyethyl)azetidine

HRID 1091287Notes

Reaction equation

HRID 1091287 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][CH2:19][OH:20])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:21]I.[H-].[Na+]>CN(C=O)C>[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][CH2:19][O:20][CH3:21])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 534408902-[1-(Diphenylmethyl)azetidin-3-yl]ethan-1-ol

Product 1

HCID 665916751-Benzhydryl-3-(2-methoxyethyl)azetidineYield 42.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Benzhydryl-3-(2-hydroxyethyl)azetidine (1.58 g, 5.91 mmol) was suspended in DMF (30 mL), and under a nitrogen stream, methyl iodide (0.37 mL, 5.91 mmol) and 60% sodium hydride (355 mg, 8.87 mmol) were added at 0° C. with stirring. The reaction mixture was stirred for two hours at the same temperature and then poured onto ice water, and the mixture was extracted with ethyl acetate. The combined extract was washed with ice water and saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure. The obtained residue was purified by flash chromatography (Flash Chromatography System from Biotage AB, column size: 40M, ethyl acetate:n-hexane=5:95), to obtain the title compound (700 mg, 42%) as an oily matter.

Workup

  1. stirringThe reaction mixture was stirred for two hours at the same temperature
  2. additionpoured onto ice water
  3. extractionthe mixture was extracted with ethyl acetate
  4. extractionThe combined extract
  5. washwas washed with ice water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationthe solvent was concentrated under reduced pressure
  8. customThe obtained residue was purified by flash chromatography (Flash Chromatography System from Biotage AB, column size: 40M, ethyl acetate:n-hexane=5:95)

Sources & evidence

ORD record
ord-9c88a3d0c9814509a9e9faed51cefa4a
Source dataset
uspto-grants-2012_03
Patent number
US08129366B2

Reaction notes

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