Hexane → 1'-Benzyl-5-fluoro-3H-spiro[2-benzofuran-1,4'-piperidin]-3-one

To a stirred solution of 2-bromo-5-fluorobenzoic acid (5.0 g, 21.9 mmol) at −70° C. in tetrahydrofuran (30 ml) was added dropwise a 1.6M n-butyllithium solution in hexane (44 ml, 70.1 mmol) over a period of 1 hour. After 3 hours, a solution of 1-benzyl-4-piperidone (8.5 g, 43.8 mmol) in tetrahydrofuran (20 ml) was added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. The mixture was poured into a stirred mixture of water (150 ml) and ether (150 ml). The aqueous layer was extracted with ether (2×40 ml), acidified with HCl 5 N (20 ml) to pH 2 and boiled for 1 hour. The mixture was cooled to 0° C., basified (pH 10) with NaOH 5 N and rapidly extracted with dichloromethane (3×80 ml). The combined extracts were washed with water (80 ml), dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was chromatographed on silica gel (eluent: heptane/ethylacetate 1:1) to yield 2.27 g (33%) of 1′-benzyl-5-fluoro-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one as light yellow solid. MS m/e: 312 (M+H+).

1. extractionThe aqueous layer was extracted with ether (2×40 ml)
2. waitboiled for 1 hour
3. temperatureThe mixture was cooled to 0° C.
4. extractionrapidly extracted with dichloromethane (3×80 ml)
5. washThe combined extracts were washed with water (80 ml)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude oil was chromatographed on silica gel (eluent: heptane/ethylacetate 1:1)

ORD record

ord-ddd7ad6be5dc4791bed650f040886ed4

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664216B2