1-Bromo-4-iodobenzene → Tert-butyl 3-(4-bromophenyl)-3-hydroxyazetidine-1-carboxylate

Temperature

-78 °C

Into a 1-L 3-necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1-bromo-4-iodobenzene (25.0 g, 88.4 mmol) in tetrahydrofuran/diethyl ether (400/200 mL). The solution was cooled to −78° C. then n-BuLi (2.5 M, 37.1 mL, 92.8 mmol) was added drop-wise over 10 min. To the resulting mixture was added tert-butyl 3-oxoazetidine-1-carboxylate (16.6 g, 97.0 mmol) in THF (100 mL) drop-wise at −78° C. The resulting mixture was stirred for 1.5 h at −78° C., then carefully quenched with water (300 mL). The aqueous phase was extracted with ethyl acetate (200 mL) and the combined organic layers were washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:20-1:5) as the eluent followed by re-crystallized from ethyl acetate:PE in the ratio of 1:100 to yield 8.0 g (28%) of the title compound as a white solid.

1. customInto a 1-L 3-necked round-bottom flask, purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. customcarefully quenched with water (300 mL)
4. extractionThe aqueous phase was extracted with ethyl acetate (200 mL)
5. washthe combined organic layers were washed with brine (2×100 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:20-1:5) as the eluent
10. customby re-crystallized from ethyl acetate

ORD record

ord-1bb6b5ece3d24247bd28364adf15f30e

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2