Methyl iodide → 1-Benzhydryl-3-methoxyazetidine

HRID 985291Notes

Reaction equation

HRID 985291 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([OH:18])[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.[H-].[Na+].[CH3:21]I>CN(C=O)C>[CH:1]([N:14]1[CH2:17][CH:16]([O:18][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 3304481-(Diphenylmethyl)azetidin-3-ol

Product 1

HCID 5975241-Benzhydryl-3-methoxyazetidineYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To an ice cold solution of 1-benzhydrylazetidin-3-ol 9a (1.0 g, 4.2 mmole) in DMF (10 ml) was added 60% dispersion NaH in mineral oil (0.25 g, 6.3 mmole). After 30 min at 0° C., 5 ml more DMF was added along with methyl iodide (0.39 ml, 6.3 mmole). The ice bath was removed, and the reaction was stirred at room temperature (rt). After 1.5 hr, the reaction was poured into brine and extracted with Et2O (2×). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was flash chromatographed on silica gel eluting Hexanes/EtOAc (1:1) to give 919 mg (92%) of a colorless oil which crystallized on standing. 1H NMR (DMSO-d6) δ7.42 (4H, d, J=7.3 Hz), 7.27 (4H, t, J=7.3 Hz), 7.13 (2H, t, J=7.3 Hz), 4.39 (1H, s), 3.95 (1H, p, J=5.8 Hz), 3.35 (2H, t, J=6.3 Hz), 3.11 (3H, s), 2.75 (2H, t, J=5.6 Hz).

Workup

  1. customThe ice bath was removed
  2. waitAfter 1.5 hr
  3. additionthe reaction was poured into brine
  4. extractionextracted with Et2O (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customchromatographed on silica gel
  9. washeluting Hexanes/EtOAc (1:1)

Sources & evidence

ORD record
ord-2d2efc7f8bdd497fba1f90fea564fb6c
Source dataset
uspto-grants-2005_03
Patent number
US06869962B2

Reaction notes

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