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

HRID 2265706Notes

Reaction equation

HRID 2265706 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 while cooling in an ice bath. A solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (5.00 g) in tetrahydrofuran (50 ml) was gradually added thereto, followed by stirring at the same temperature for 30 min. Then, the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was again stirred while cooling in an ice bath for 15 min. To the reaction mixture was added dropwise iodomethane (3.09 ml), followed by stirring for 2 hr. 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 layer was combined, washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:1, 2:1, 1:1, then ethyl acetate). Fractions containing the target compound were concentrated to provide the titled compound as a colorless oil (1.80 g, 33.3%). Fractions containing the starting material were concentrated for recovery (2.10 g, 42.0%).

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringby stirring at the same temperature for 30 min
  3. stirringThen, the reaction mixture was stirred at room temperature for 30 min
  4. stirringThe reaction mixture was again stirred
  5. temperaturewhile cooling in an ice bath for 15 min
  6. stirringby stirring for 2 hr
  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. customThe solvent was removed
  13. customthe residue was purified by silica gel column chromatography (eluent
  14. additionFractions containing the target compound
  15. concentrationwere concentrated

Sources & evidence

ORD record
ord-d3590f371e074263b6e89ff823294136
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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