Methyl Acrylate → 1-(1,1-Dimethylethyl) 3-(2-carboxyethoxy)-1-azetidinecarboxylate

A mixture of 3-hydroxyazetidine-1-carboxylic acid tert-butyl ester (350 mg, 2.0 mmol) and NaH (6 mg of a 60% dispersion in mineral oil, 0.15 mmol) was warmed until effervescence had ceased. The mixture was stirred at ambient temperature for 15 min, then methyl acrylate (940 μL, 10.5 mmol) was added. After 3 h, the reaction was diluted with Et2O (50 mL), before being washed with H2O (10 mL) and brine (10 mL) then dried (MgSO4). The Et2O solution was filtered and evaporated, then EtOAc (15 mL) was added. The solvents were removed, then more EtOAc (15 mL) was added, before being evaporated off again to ensure that no methyl acrylate remained. The residue was dissolved in MeOH (3 mL), before being treated with 2 M NaOH (2.0 mL). After 1 h, the MeOH was removed, then H2O (12 mL) and Et2O (10 mL) were added. The Et2O layer was extracted further with H2O (8 mL), then the combined aqueous extracts were acidified to pH 2 with 2 M HCl and the resulting mixture extracted with EtOAc (50+40 mL). The combined organic extracts were washed with brine and dried (MgSO4). Filtration, solvent evaporation and column chromatography (IH-EtOAc, 1:1) gave the title compound: δC (CDCl3): 28.1, 34.8, 56.3, 63.9, 68.0, 79.9, 156.4, 176.2.

1. temperaturewas warmed until effervescence
2. waitAfter 3 h
3. washbefore being washed with H2O (10 mL) and brine (10 mL)
4. dry with materialthen dried (MgSO4)
5. filtrationThe Et2O solution was filtered
6. customevaporated
7. additionEtOAc (15 mL) was added
8. customThe solvents were removed
9. additionmore EtOAc (15 mL) was added
10. custombefore being evaporated off again
11. dissolutionThe residue was dissolved in MeOH (3 mL)
12. additionbefore being treated with 2 M NaOH (2.0 mL)
13. waitAfter 1 h
14. customthe MeOH was removed
15. additionH2O (12 mL) and Et2O (10 mL) were added
16. extractionThe Et2O layer was extracted further with H2O (8 mL)
17. extractionthe resulting mixture extracted with EtOAc (50+40 mL)
18. washThe combined organic extracts were washed with brine
19. dry with materialdried (MgSO4)
20. filtrationFiltration, solvent evaporation and column chromatography (IH-EtOAc, 1:1)

ORD record

ord-0e16ed32ad294867836660e4fa7b54b3

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08193359B2