Tetrahydrofuran → HCID 66735542, compound

Temperature

0 °C

A 250 ml round bottom flask containing 5-fluoro-6-methylpyridine-2-carbonitrile (Method 15; 2.24 g, 16.45 mmol) was charged with anhydrous THF (20 ml) under N2. The solution was cooled to 0° C., and a solution of MeMgBr (8.5 ml of a 3.0 M solution in ether, 25.5 mmol) was added dropwise. After 1 hour at 0° C., the reaction was quenched with saturated NH4Cl (10 ml, added drop wise), and the biphasic mixture was allowed to stir at 0° C. for 10 minutes. The layers were then separated, and the aqueous portion was extracted with EtOAc, and the combined organics were washed with brine, dried, filtered, and concentrated. The resulting oil was dissolved in MeOH (20 ml), and the solution was cooled to 0° C. NaBH4 (634 mg, 16.8 mmol) was added in portions over 5 minutes. The reaction was allowed to stir at room temperature for 1 hour, and was then concentrated. The residue was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried, filtered, and concentrated. The crude material was purified by silica gel chromatography (Rf in 60:40 hexanes:EtOAc=0.42) to afford the title compound as a pale yellow oil (550 mg, 22% over two steps). 1H NMR (400 MHz, CDCl3) δ 1.46 (d, J=6.6 Hz, 3H), 2.51 (d, J=3.0 Hz, 3H), 4.10 (s, 1H), 4.79-4.87 (m, 111), 7.08 (dd, J=8.5, 3.7 Hz, 1H), 7.31 (t, J=8.7 Hz, 1H).

1. customthe reaction was quenched with saturated NH4Cl (10 ml
2. additionadded drop wise), and the biphasic mixture
3. customThe layers were then separated
4. extractionthe aqueous portion was extracted with EtOAc
5. washthe combined organics were washed with brine
6. customdried
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe resulting oil was dissolved in MeOH (20 ml)
10. temperaturethe solution was cooled to 0° C
11. stirringto stir at room temperature for 1 hour
12. concentrationwas then concentrated
13. customThe residue was partitioned between EtOAc and H2O
14. extractionthe aqueous layer was extracted with EtOAc
15. washThe combined organics were washed with brine
16. customdried
17. filtrationfiltered
18. concentrationconcentrated
19. customThe crude material was purified by silica gel chromatography (Rf in 60:40 hexanes:EtOAc=0.42)

ORD record

ord-48f6de1be1a04eed85d6771e6b80a5b1

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114989B2