Tetrahydrofuran → 5-Ethyl-2-fluoropyridine-3-carbaldehyde
Reaction equation
[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([F:9])=[N:7][CH:8]=1)[CH3:2].[O:10]1CCC[CH2:11]1>>[CH2:1]([C:3]1[CH:4]=[C:5]([CH:11]=[O:10])[C:6]([F:9])=[N:7][CH:8]=1)[CH3:2]Participants
3
Procedure
A solution of diisopropylainine (1.01 mL, 7.19 mmol) in tetrahydrofuran (20 mL) was treated in ice-bath with n-butyllithiuin (2.5M, 2.9 mL, 7.19 mmol) and stirred for 30 min. The resulting solution was reacted at −78° C. with 5-ethyl-2-fluoropyridine (2-b, 0.75 g, 5.99 mmol), stirred for 4 h, and treated with N,N-dimethylforninamide (482 mg, 6.59 mmol). The reaction mixture was quenched with acetic acid (1 mL), partitioned between ethyl acetate and water. The organic layer was washed with 0.5N—HCl and then with brine, separated, dried (MgSO4) and concentrated in vacuo. Chromatography (30% ethyl acetate in hexanes) afforded the desired compound (2-f); 1H NMR (500 MHz, CDCl3) δ10.3 (s, 1H), 8.29 (d, 1H, J=2.0 Hz), 8.12 (dd, 1H, J=9.0, 2.5 Hz), 2.73 (q, 2H, J =7.8 Hz), 1.29 (t, 3H, J=7.5 Hz).
Workup
- stirringstirred for 4 h