Tetrahydrofuran → 5-Ethyl-2-fluoro-3-pyridinecarboxaldehyde

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).

1. stirringstirred for 4 h
2. additiontreated with N,N-dimethylforninamide (482 mg, 6.59 mmol)
3. customThe reaction mixture was quenched with acetic acid (1 mL)
4. custompartitioned between ethyl acetate and water
5. washThe organic layer was washed with 0.5N—HCl
6. customwith brine, separated
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo

ORD record

ord-d20b439877d34707b5636982f854b301

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07629367B2