反应详情

温度

-15 °C

To a solution of 4-bromo-2-(chloromethyl)-1-iodobenzene (2.0 g, 6.04 mmol, 1 eq) in THF (16 mL), isopropylmagnesium chloride lithium chloride complex (5.11 mL, 1.3M in THF, 1.1 eq) was added over about 5 min while the internal temperature didn't exceed −15° C. Reaction is stirred at −15° C. for 30 min. Then a solution of 1-Boc-3-azetidinone (1.24 g, 1.2 eq) in THF (4 mL) was added dropwise; internal temperature at −30° C. The reaction is stirred at room temperature overnight. Reaction was quenched with a solution of citric acid (14 mL of 1M). This was extracted with MTBE and organic layer was washed with aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude yellow oil is submitted to silica gel column chromatography (0 to 50% ethyl acetate in heptane). 1.6 g of tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate was obtained.

1. customexceed −15° C
2. customReaction
3. customat −30° C
4. stirringThe reaction is stirred at room temperature overnight
5. customReaction
6. customwas quenched with a solution of citric acid (14 mL of 1M)
7. extractionThis was extracted with MTBE and organic layer
8. washwas washed with aqueous NaHCO3 and brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure