Furan → HCID 15480239, compound

Temperature

-78 °C

To a solution of furan (1.45 mL, 20.0 mmol) in THF (30.0 mL) was added sec-butyllithium (1.3M, 7.69 mL, 10.0 mmol) at -78° C. After half an hour at this temperature, trimethyl borate (2.27 mL, 20.0 mmol) was added. The reaction mixture was stirred at -78° C. for one hour and slowly warmed up to room temperature. Solvent was removed, and benzene (10.0 mL), sodium carbonate (2.0M, 5.0 mL), tetraids(triphenylphosphine)palladium(0) (175 mg) and 5-bromo-3-(1- methyl-2-(S)-pyrrolidinylmethoxy)pyridine (1.36 g, 5.0 mmol) were added. The reaction mixture was refluxed overnight, then cooled to room temperature. Water (2 mL) was added, and solid sodium bicarbonate was added until the aqueous layer was saturated. The mixture was extracted with EtOAc, which was dried over MgS04, filtered and concentrated. The residue was chromatographed on a silica gel column, eluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90 to afford an oil (1.27 g, 99%). MS (CI/NH3) m/z 259 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.70-2.22 (m, 4H), 2.28-2.40 (m, 1H), 2.51 (s, 3H), 2.66-2.75 (m, 1H), 3.10-3.18 (m, 1H), 3.97-4.11 (m, 2H), 6.51 (dd, J=4.8 Hz, J=3.6 Hz, 1H), 6.74 (d, J=4.9 Hz,, 1H), 7.47 (dd, J=3.0 Hz, J=2.1 Hz, 1H), 7.53 (d, J=3.6 Hz, 1H), 8.22 (d, J=3.0 Hz, 1H), 8.54 (d, J=2.1 Hz, 1H).

1. temperatureslowly warmed up to room temperature
2. customSolvent was removed
3. temperatureThe reaction mixture was refluxed overnight
4. temperaturecooled to room temperature
5. extractionThe mixture was extracted with EtOAc, which
6. customwas dried over MgS04
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was chromatographed on a silica gel column
10. washeluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90

ORD record

ord-bf436d996d5b447c9b747e75eda9ac69

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06127386