N-bromobutanimide → 3-Bromo-4-oxochroman-7-carbonitrile

Temperature

-30 °C

4-Oxochroman-7-carbonitrile (11.0 g, 63.5 mmol) was dissolved in THF (250 mL) and cooled to −30° C. prior to the addition of LiHMDS (66.7 mL, 66.7 mmol) dropwise. The resulting solution was stirred for 20 min. Next, the temperature was lowered to −78° C. and the solution was stirred for 0.5 h. In another flask, NBS (11.3 g, 63.5 mmol) was dissolved in THF (250 mL) and cooled to −78° C. Then the anion solution was transferred into NBS/THF solution at −78° C. via cannula. The resulting solution was stirred at −78° C. for 40 min. The reaction was quenched with aqueous saturated NH4Cl solution and extracted with EtOAc twice. The combined organic layers were washed with 1N HCl, brine, dried (MgSO4), and filtered. The filtrate was concentrated and the resulting residue was purified by flash chromatography with 10% to 20% EtOAc/hexane on 120 g ISCO column to afford 3-bromo-4-oxochroman-7-carbonitrile (10.0 g, 39.7 mmol, 62.5% yield) as a pale yellow solid: LCMS=251.9 [M+H]+.

1. customwas lowered to −78° C.
2. stirringthe solution was stirred for 0.5 h
3. temperaturecooled to −78° C
4. stirringThe resulting solution was stirred at −78° C. for 40 min
5. customThe reaction was quenched with aqueous saturated NH4Cl solution
6. extractionextracted with EtOAc twice
7. washThe combined organic layers were washed with 1N HCl, brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationThe filtrate was concentrated
11. customthe resulting residue was purified by flash chromatography with 10% to 20% EtOAc/hexane on 120 g ISCO column

ORD record

ord-faa41c0e55c34a6d99bd98746c4d4efc

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629282B2