Water → Tert-butyl 3-(4-benzyloxybutoxy)-3-o-tolylazetidine-1-carboxylate

HRID 530697Notes

Reaction equation

HRID 530697 reaction equation
[OH:1][C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[H-].[Na+].[CH2:22]([O:29][CH2:30][CH2:31][CH2:32][CH2:33]Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C)C=O>[CH2:22]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][O:1][C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 4422181((4-Bromobutoxy)methyl)benzeneHCID 65919621Tert-butyl 3-hydroxy-3-(2-methylphenyl)azetidine-1-carboxylate

Product 1

HCID 71152233Tert-butyl 3-(4-benzyloxybutoxy)-3-o-tolylazetidine-1-carboxylateYield 88.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1 g (3.79 mmol) of tert-butyl 3-hydroxy-3-o-tolylazetidine-1-carboxylate dissolved in 5 ml of N,N-dimethylformamide is added dropwise to a suspension of 455 mg (11.4 mmol) of 60% sodium hydride in oil, precooled to 20° C. After stirring for 15 minutes, 2.77 g (11.4 mmol) of 4-benzyloxybutyl bromide are added and stirring is continued for 15 hours at room temperature. The reaction medium is hydrolysed with water and then extracted with ethyl acetate. The organic phase is washed three times with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel eluted with a heptane/ethyl acetate mixture, the polarity being increased from 100/0 to 90/00. 1.43 g of tert-butyl 3-(4-benzyloxybutoxy)-3-o-tolylazetidine-1-carboxylate are obtained in the form of a colourless oil in a yield of 80%.

Workup

  1. customprecooled to 20° C
  2. stirringstirring
  3. waitis continued for 15 hours at room temperature
  4. extractionextracted with ethyl acetate
  5. washThe organic phase is washed three times with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue obtained
  10. customis purified by chromatography on silica gel
  11. washeluted with a heptane/ethyl acetate mixture
  12. temperaturethe polarity being increased from 100/0 to 90/00

Sources & evidence

ORD record
ord-fad53fed2b9d4d9a87c5ab714831530d
Source dataset
uspto-grants-2016_05
Patent number
US09353083B2

Reaction notes

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