Acetic Acid → 1-Benzyl-2-methyl-azetidine-2-carboxylic acid ethyl ester

Temperature

-76 °C

A solution of 2-[benzyl-(2-chloro-ethyl)-amino]-propionic acid ethyl ester (27.4 g, 1 eq.) in 253 mL of dry THF was cooled to −78° C. under argon. KHMDS (15% w/w in toluene, 170.40 g, 1.25 eq.) was slowly added so that temperature was kept below −76° C. The reaction was stirred for 1 h at −76° C., then warmed to 20° C. and stirred for 1 h. Acetic acid (1.74 mL, 0.3 eq.) was added and the reaction was stirred at 20° C. for 10 min. The reaction was quenched with 50 mL of a saturated aqueous solution of NaHCO3 and partially concentrated under reduced pressure. The crude was extracted three times with DCM. The organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with heptane/EtOAc 100/0 to 90/10) to afford 1-benzyl-2-methyl-azetidine-2-carboxylic acid ethyl ester (18.75 g, yield=79%).

1. customwas kept below −76° C
2. temperaturewarmed to 20° C.
3. stirringstirred for 1 h
4. stirringthe reaction was stirred at 20° C. for 10 min
5. customThe reaction was quenched with 50 mL of a saturated aqueous solution of NaHCO3
6. concentrationpartially concentrated under reduced pressure
7. extractionThe crude was extracted three times with DCM
8. dry with materialThe organic layers were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe crude was purified by chromatography on silica gel (elution with heptane/EtOAc 100/0 to 90/10)

ORD record

ord-65c762b0dd89495094b35cd4931ca45d

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759334B2