Trifluoroacetic acid → 4-(Difluoromethyl)pyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

A flask containing N-tert-butyl-4-(difluoromethyl)pyridin-2-amine (4.43 g, 22.1 mmol), triethylsilane (7.28 mL, 44.2 mmol) and trifluoroacetic acid (22.1 mL, 1 M) was fitted with a reflux condenser. The reaction mixture was stirred at 90° C. for 21 hr and then, after cooling to rt, concentrated to dryness and partitioned between CH2Cl2 and sat. aq. NaHCO3. After separation of the phases, the aqueous layer was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4. Concentration afforded 4-(difluoromethyl)pyridin-2-amine as a light brown solid (3.16 g, >99%); 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J=5.3 Hz, 1H), 6.74 (d, J=5.3 Hz, 1H), 6.66-6.33 (m, 2H), 4.62 (br s, 2H).

Provenance & Evidence