2-Bromobenzoic acid → 1'-Benzyl-3H-spiro[isobenzofuran-1,4'-piperidin]-3-one

A solution of 2-bromobenzoic acid (20.12 g, 0.1 mol) in THF (200 mL) was treated dropwise with n-BuLi (2.5 M, 80 mL) at −78° C. The mixture was stirred at this temperature for 30 min, followed by dropwise addition of a solution of N-benzylpiperdine-4-one (26 g, 137 mmol) in THF (100 mL). The resulting mixture was stirred at −78° C. for 30 min, and was then allowed to warm to room temperature and stirred overnight. The reaction was quenched with water (100 mL) and the resulting mixture was washed with ether (100 mL). The aqueous layer was refluxed for 1 hr and then acidified to pH 2.5. The mixture was extracted with CHCl3 (3×50 mL), the combined organic layers were washed with brine, dried over Na2SO4 and concentrated to dryness to obtain 1′-benzyl-3H-spiro[isobenzofuran-1,4′-piperidin]-3-one 1b (6 g).

1. stirringThe resulting mixture was stirred at −78° C. for 30 min
2. stirringstirred overnight
3. customThe reaction was quenched with water (100 mL)
4. washthe resulting mixture was washed with ether (100 mL)
5. temperatureThe aqueous layer was refluxed for 1 hr
6. extractionThe mixture was extracted with CHCl3 (3×50 mL)
7. washthe combined organic layers were washed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated to dryness

ORD record

ord-eafacdc9da374da4b97e44dc82c3b064

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863449B2