Ethyl Acetate → 2-(1-((Tert-butoxy)carbonyl)-3-hydroxyazetidin-3-yl)acetic acid

Temperature

0 °C

LHMDS (6.43 mL of 1N solution in THF) was cooled to −78° C. Ethyl acetate (0.63 mL, 6.43 mmol) was added and the reaction mixture was stirred for 10 minutes. tert-Butyl 3-oxoazetidine-1-carboxylate (1 g, 5.84 mmol) was added to the mixture and the reaction was stirred for 15 minutes. The reaction mixture was warmed to 0° C. and was then quenched with water (25 mL). The reaction mixture was extracted with ether. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated. The remaining oil was dissolved in MeOH (25 mL) and 1N NaOH (15 mL) was added and the mixture was stirred at room temperature overnight. This was concentrated in vacuo to remove MeOH and then to the remaining aqueous solution was added 1N HCl (100 mL). This mixture was extracted with CH2Cl2 (100 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated to afford the title intermediate (215 mg) as an oil.

1. stirringthe reaction was stirred for 15 minutes
2. customwas then quenched with water (25 mL)
3. extractionThe reaction mixture was extracted with ether
4. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe remaining oil was dissolved in MeOH (25 mL)
8. addition1N NaOH (15 mL) was added
9. stirringthe mixture was stirred at room temperature overnight
10. concentrationThis was concentrated in vacuo
11. customto remove MeOH
12. additionto the remaining aqueous solution was added 1N HCl (100 mL)
13. extractionThis mixture was extracted with CH2Cl2 (100 mL)
14. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
15. filtrationfiltered
16. concentrationconcentrated

ORD record

ord-f3cdc19ec1084052adef1e30a8fe1e98

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08742110B2