1-Bromo-3-fluorobenzene → HCID 57893670, Verbindung

Dissolve 1-benzyl-cis-3-methyl-piperidin-4-ol (preparation 6, 3.84 g, 18.73 mmol) in dry N,N-dimethylformamide (100 mL), treat with 60% sodium hydride (1.05 g, 26.22 mmol), heat and stir at 80° C. After 1 hr., add-1-bromo-3-fluoro-benzene (2.51 mL, 22.45 mmol), stir and heat at 110° C. After 16 hr., cool to ambient temperature. Partition between water (100 mL) and ethyl acetate (100 mL), wash the aqueous layer with ethyl acetate (2×100 mL), combine the organic layers, wash with water (5×100 mL) and aqueous NaCl solution (100 mL). Dry the organic layer over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 2% (2M NH3/methanol)/methylene dichloride to obtain the title compound as a mixture of enantiomers (1.69 g, 24%). 1H NMR (CDCl3): 7.3 (m, 5H), 7.1 (m, 3H), 6.8 (m, 1H), 4.3 (m, 1H), 3.5 (d, 2H), 2.5 (m, 2H), 2.4 (m, 2H), 2.0 (m, 2H), 1.8 (m, 1H), 1.0 (d, 3H).

1. temperatureheat
2. stirringstir
3. temperatureheat at 110° C
4. waitAfter 16 hr
5. temperature, cool to ambient temperature
6. customPartition between water (100 mL) and ethyl acetate (100 mL)
7. washwash the aqueous layer with ethyl acetate (2×100 mL)
8. washwash with water (5×100 mL) and aqueous NaCl solution (100 mL)
9. dry with materialDry the organic layer over sodium sulfate
10. filtrationfilter
11. concentrationconcentrate
12. customPurify the residue by silica gel flash chromatography
13. washeluting with 2% (2M NH3/methanol)/methylene dichloride

ORD-Eintrag

ord-f100d98cfb044d30bd580fbf503b7211

Quelldatensatz

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07608629B2