Ammonia → 2-(3,5-Dichloropyridin-2-yl)-2,2-difluoroethanamine

Temperatur

0 °C

To a solution of 1.3 g (5.7 mmol) of 2-(3,5-dichloropyridin-2-yl)-2,2-difluoroethanol (Int-9) in dry acetonitrile under argon, were added 0.744 mL (9.12 mmol) of dry pyridine. The reaction mixture was cooled to 0° C. and 1.06 mL (6.27 mmol) of triflic anhydride were added dropwise in 15 min while maintaining the temperature below 8° C. The reaction mixture was stirred at 0° C. for additional 30 min 9.9 mL of a 28% w/w aqueous solution of ammonia (144 mmol) were added and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was diluted with 50 mL of brine and the product extracted three times with 25 mL of ethyl acetate. The organic phases were collected, washed three times with 40 mL of brine and dried over magnesium sulfate. Afater evaporation of the solvent under vacuum 1.09 g of brown oil were obtained. After purification by column chromatography on silica gel (heptane/ethyl acetate gradient) 0.65 g (50%) of 2-(3,5-dichloropyridin-2-yl)-2,2-difluoroethanamine (IIa-15) were obtained as a yellow oil, (M+1)=227, 19F-NMR (235 MHz, CDCl3) δ (ppm): −104.80 (CF2).

1. temperaturewhile maintaining the temperature below 8° C
2. additionwere added
3. extractionthe product extracted three times with 25 mL of ethyl acetate
4. customThe organic phases were collected
5. washwashed three times with 40 mL of brine
6. dry with materialdried over magnesium sulfate
7. customAfater evaporation of the solvent under vacuum 1.09 g of brown oil
8. customwere obtained
9. customAfter purification by column chromatography on silica gel (heptane/ethyl acetate gradient) 0.65 g (50%) of 2-(3,5-dichloropyridin-2-yl)-2,2-difluoroethanamine (IIa-15)
10. customwere obtained as a yellow oil, (M+1)=227, 19F-NMR (235 MHz, CDCl3) δ (ppm): −104.80 (CF2)

ORD-Eintrag

ord-c61291753ad542e88fa478e82e99aa6e

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09301526B2