Ammonium Chloride → 1-[1-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-ethylamine

Temperature

-48 °C

412 mg of 2-methyl-propane-2-sulfinic acid 1-[1-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-methylideneamide (step 3) was dissolved in 12 ml of dichloromethane and cooled to −48° C. 0.78 ml of methylmagnesium bromide (3M solution in diethyl ether) was added dropwise at −48° C. The reaction mixture was left to warm to ambient temperature and stirred for 18 hours. Then the mixture was poured into 30 ml of a saturated aqueous ammonium chloride solution. The aqueous phase was extracted with three 30 ml portions of ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was dissolved in 12 ml of methanol and 0.6 ml of hydrochloric acid (4M solution in dioxane) was added. The mixture was stirred at ambient temperature for 2 hours, then concentrated. The residue was treated with aqueous 1N hydrochloric acid and washed with ethyl acetate. The aqueous phase was made basic by addition of aqueous sodium hydroxide solution, then extracted with ethyl acetate. The organic phase dried over sodium sulfate, filtered and concentrated. Thus, 262 mg of 1-[1-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-ethylamine was obtained as a yellow oil. 1H-NMR (CDCl3): 8.72 ppm (s, 1H), 7.90 ppm (s, 1H), 3.10 ppm (q, 1H), 1.34 ppm (s, 2H, broad), 1.06 ppm (d, 3H), 1.02 ppm (m, 2H), 0.93 ppm (m, 2H).

1. waitThe reaction mixture was left
2. temperatureto warm to ambient temperature
3. extractionThe aqueous phase was extracted with three 30 ml portions of ethyl acetate
4. dry with materialThe organic phase was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in 12 ml of methanol
8. addition0.6 ml of hydrochloric acid (4M solution in dioxane) was added
9. stirringThe mixture was stirred at ambient temperature for 2 hours
10. concentrationconcentrated
11. additionThe residue was treated with aqueous 1N hydrochloric acid
12. washwashed with ethyl acetate
13. additionThe aqueous phase was made basic by addition of aqueous sodium hydroxide solution
14. extractionextracted with ethyl acetate
15. dry with materialThe organic phase dried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated

ORD record

ord-19b31f0c48b742fa84dae7d8b7bac3be

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040708B2