Methyl iodide → 1-Benzhydryl-2-(alpha-methylaminobenzyl)azetidine

HRID 46458Notes

Reaction equation

HRID 46458 reaction equation
[CH:1]([N:14]1[CH2:17][CH2:16][CH:15]1[CH:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=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+].[CH3:28]I>CN(C)C=O>[CH:1]([N:14]1[CH2:17][CH2:16][CH:15]1[CH:18]([NH:25][CH3:28])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=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 203452731-Benzhydryl-2-(alpha-aminobenzyl)azetidine

Product 1

HCID 203452871-Benzhydryl-2-(alpha-methylaminobenzyl)azetidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-25 °C

Procedure

To a stirred solution of 2.50 g of 1-benzhydryl-2-(α-aminobenzyl)azetidine in 25 ml. of N,N-dimethylformamide, add 365 mg. of a 55% dispension of sodium hydride. Stir the mixture under a nitrogen atmosphere and when frothing subsides, warm and maintain the stirred mixture at 40° for twenty minutes. Cool the mixture to -25° C. and add 1.20 g. of methyl iodide. Remove the reaction mixture from the cooling bath and allow it to warm to room temperature. After ca. 15 minutes at room temperature, pour the contents of the reaction flask into a stirred mixture of 100 ml. of water and 25 ml. of ether. Separate the layers and re-extract the aqueous phase with ether. Combine all ether extracts, wash successively with water and brine, dry over anhydrous sodium sulfate, and strip off solvent in vacuo. Crystallize the residual solid from ether to obtain the analytically pure title compound containing 1/4 mole of water-of-crystallization and having m.p. 111°-113°.

Workup

  1. temperaturewhen frothing subsides, warm
  2. temperaturemaintain the stirred mixture at 40° for twenty minutes
  3. additionadd 1.20 g
  4. customRemove the reaction mixture from the cooling bath
  5. temperatureto warm to room temperature
  6. additionpour the contents of the reaction flask
  7. additioninto a stirred mixture of 100 ml
  8. customSeparate the layers
  9. extractionre-extract the aqueous phase with ether
  10. washwash successively with water and brine
  11. dry with materialdry over anhydrous sodium sulfate, and strip off solvent in vacuo
  12. customCrystallize the residual solid from ether

Sources & evidence

ORD record
ord-51470e56aa694d6d91b1a84d675157ce
Source dataset
uspto-grants-1979_11
Patent number
US04173566

Reaction notes

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