N-bromobutanimide → 4-(5-Bromo-7-fluoro-2,3-dihydrobenzofuran-2-yl)piperidine

To a solution of 4-(7-fluoro-2,3-dihydrobenzofuran-2-yl)piperidine hydrochloride (1.18 g, 4.58 mmol) in MeOH (36.6 mL) at 0° C. was added NBS (0.815 g, 4.58 mmol) in one portion. Upon completion of addition, the reaction mixture was immediately warmed to room temperature, where it stirred for 3 hours. At the conclusion of this period, the reaction mixture was quenched with aqueous Na2H2S2O5 (5%, 5 mL). The solvent was removed under reduced pressure to yield a residue. The residue was diluted with CH2Cl2 (5 mL), washed with NaHCO3 (aq, sat, 3 mL) and brine (3 mL). The organic layer was separated, dried (Na2SO4), filtered, and concentrated to afford Compound 3E as a colorless oil (1.3 g, 95% yield). LC/MS (m/z)=301 (M+H)+.

1. additionUpon completion of addition
2. customAt the conclusion of this period, the reaction mixture was quenched with aqueous Na2H2S2O5 (5%, 5 mL)
3. customThe solvent was removed under reduced pressure
4. customto yield a residue
5. washwashed with NaHCO3 (aq, sat, 3 mL) and brine (3 mL)
6. customThe organic layer was separated
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-661b1e523ca74fe9a83fd437f555a1fc

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729084B2