Water → tert-Butyl 3-methoxyazetidine-1-carboxylate

HRID 1712653Notes

Reaction equation

HRID 1712653 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1.I[CH3:16].O>O1CCCC1>[CH3:16][O:3][CH:4]1[CH2:5][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylate

Product 1

HCID 22243050tert-Butyl 3-methoxyazetidine-1-carboxylateYield 33.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of sodium hydride (2.89 g) in tetrahydrofuran (50 ml) was stirred with cooling in an ice bath. A solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (5.00 g) in tetrahydrofuran (50 ml) was gradually added, followed by stirring at the same temperature for 30 minutes. Then, the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was stirred with cooling in an ice bath again for 15 minutes. Iodomethane (3.09 ml) was added dropwise to the reaction mixture, followed by stirring for 2 hours. Water was gradually added to the reaction mixture. When bubbling stopped, the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:1, 2:1, 1:1, then ethyl acetate). The fractions containing the target compound were concentrated to give the title compound (1.80 g, 33.3%) as a colorless oil. The fractions containing the starting material were concentrated and collected (2.10 g, 42.0%).

Workup

  1. temperaturewith cooling in an ice bath
  2. stirringby stirring at the same temperature for 30 minutes
  3. stirringThen, the reaction mixture was stirred at room temperature for 30 minutes
  4. stirringThe reaction mixture was stirred
  5. temperaturewith cooling in an ice bath again for 15 minutes
  6. stirringby stirring for 2 hours
  7. customWhen bubbling
  8. customthe organic layer was separated
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. washwashed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled off
  13. customthe residue was purified by silica gel column chromatography (eluent
  14. additionThe fractions containing the target compound
  15. concentrationwere concentrated

Sources & evidence

ORD record
ord-37a19b5ffc1543318f41175d4dec7c8f
Source dataset
uspto-grants-2010_09
Patent number
US07790885B2

Reaction notes

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