2-Bromopyridine → 1-Pentanone,4,4,5,5,5-pentafluoro-1-(2-pyridinyl)-

Temperature

25 °C

Isopropylmagnesium chloride (2 M in THF) (1.960 mL, 3.92 mmol) was added to a stirred solution of 2-bromopyridine (0.392 mL, 4.11 mmol) in dry THF (3.73 mL) at 25° C. under N2. After 2 h at 25° C. a solution of 4,4,5,5,5-pentafluoro-N-methoxy-N-methylpentanamide (0.8781 g, 3.73 mmol) in dry THF (1.866 mL) was added via cannula and the resulting mixture was stirred at 25° C. overnight. Another 0.2 eq. of Grignard reagent was generated by same procedure as above and added to reaction via cannula and the reaction was stirred for 1 h. Another 0.6 eq. of Grignard reagent was generated by same procedure as above and added to reaction via cannula and the reaction was stirred for 1 h. The reaction was quenched by the addition of saturated aq. NH4Cl and the resulting mixture was extracted with EtOAc (3×). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by silica gel chromatography using a hexanes/EtOAc gradient to afford the desired product, as an oil. 1H NMR (500 MHz, CHCl3-d): δ 8.69 (d, J=4.8 Hz, 1H); 8.05 (d, J=7.9 Hz, 1H); 7.85 (dt, J=9.1, 3.7 Hz, 1H); 7.48 (d, J=7.7 Hz, 1H); 3.56 (t, J=7.8 Hz, 2H); 2.56-2.50 (m, 2H). m/z=254.0 (M+H).

1. additionadded to reaction via cannula
2. stirringthe reaction was stirred for 1 h
3. additionadded to reaction via cannula
4. stirringthe reaction was stirred for 1 h
5. customThe reaction was quenched by the addition of saturated aq. NH4Cl
6. extractionthe resulting mixture was extracted with EtOAc (3×)
7. dry with materialThe combined extracts were dried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customto give the crude product
10. customThis was purified by silica gel chromatography

ORD record

ord-190e841e39184eebbdc5283820936589

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365574B2