Dimethyl Sulfoxide → 3-Oxo-azetidine-1-carboxylic acid tert-butyl ester

HRID 1672877Notes

Reaction equation

HRID 1672877 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1.C(N(CC)CC)C>ClCCl.O>[O:11]=[C:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylate

Product 1

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of oxalyl chloride (545 μL, 6.36 mmol) in dichloromethane (25 mL) was cooled to −78° C. While maintaining an internal temperature of −78° C., the dropwise addition of DMSO (903 μL, 12.7 mmol) followed by 1,1-dimethylethyl 3-hydroxyazetidine-1-carboxylate (1 g, 5.78 mmol in 30 mL of dichloromethane) and finally triethylamine (3.25 mL, 23.1 mmol in 20 mL of dichloromethane) was performed. The mixture was allowed to warm to room temperature and was stirred for 15 hours. The reaction mixture was diluted with water and partitioned and the organic portion was washed twice with water. The combined aqueous portion was extracted once with dichloromethane. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was purified by column chromatography. Eluting with 30% ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 893 mg, 5.20 mmol (90%) of 1,1-dimethylethyl 3-oxoazetidine-1-carboxylate as a colorless oil, which solidified upon standing. 1H NMR (400 MHz, DMSO): 4.67 (s, 4H), 1.42 (s, 9H). GC/MS for C8H13NO3: 171.

Workup

  1. temperatureto warm to room temperature
  2. custompartitioned
  3. washthe organic portion was washed twice with water
  4. extractionThe combined aqueous portion was extracted once with dichloromethane
  5. washThe combined organic portion was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a yellow oil which
  10. customwas purified by column chromatography
  11. washEluting with 30% ethyl acetate in hexanes
  12. customisolated product
  13. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-b023d43d10b34a2eb1b914ebdeaf6b6f
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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