反应详情

3-Hydroxymethylfuro[2,3-b]pyridine (101.5 mg, 0.681 mmol) was treated with thionyl chloride (2 ml) and the solution stirred at room temperature for an hour. The mixture was concentrated in vacuo, toluene added (5 ml) and evaporated to dryness. The residue was dissolved in anhydrous dimethylformamide (5 ml), potassium carbonate (0.47 g, 3.40 mmol) and 4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine hydrochloride (173.3 mg, 0.753 mmol) were added and the mixture stirred at room temperature, under nitrogen, overnight (19 hours). The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate (2×25 ml). The extracts were washed with brine (25 ml), combined, dried (MgSO4) and the residue after evaporation purified by flash chromatography, eluting with 1:1 then 2:1 ethyl acetate/hexane, to afford the title compound (118.3 mg, 54%) as a pale yellow solid. Recrystallisation from ethyl acetate/hexane gave yellow plates, m.p. 115.5°-116.5° C.; (Found: C, 70.06; H, 5.19; N, 8.52. C19H17ClN2O requires C, 70.26; H, 5.28; N, 8.62%); δH (CDCl3) 2.54 (2H, br s, tetrahydropyridinyl CH2), 2.78 (2H, t, J 5.6 Hz, tetrahydropyridinyl CH2), 3.23 (2H, m, tetrahydropyridinyl CH2), 3.78 (2H, s, ArCH2N), 6.06 (1H, t, J 3.5 Hz, tetrahydropyridinyl CH), 7.21-7.32 (5H, m, ArH), 7.68 (1H, s, 2-H), 8.12 (1H, dd, J 7.6, 1.7 Hz, 4-H), 8.34 (1H, dd, J 4.8, 1.7 Hz, 6-H); m/z (ES+) 325/327 (M+1)+.

1. concentrationThe mixture was concentrated in vacuo, toluene
2. additionadded (5 ml)
3. customevaporated to dryness
4. dissolutionThe residue was dissolved in anhydrous dimethylformamide (5 ml)
5. stirringthe mixture stirred at room temperature, under nitrogen, overnight (19 hours)
6. extractionextracted with ethyl acetate (2×25 ml)
7. washThe extracts were washed with brine (25 ml)
8. dry with materialdried (MgSO4)
9. customthe residue after evaporation
10. custompurified by flash chromatography
11. washeluting with 1:1