Triethylamine → 2,3,6-Trifluoropyridin-4-amine

Participants

Reaction Steps

A suspension of 4-amino-3-chloro-2,5,6-trifluoropyridine (2, 19.7 g, 108 mmol), 10% Pd/C (1.8 g) and triethylamine (20 mL, 140 mmol) in 150 mL of anhydrous ethanol was hydrogenated at 50 psi in a Parr hydrogenation apparatus until TLC showed the reaction was completed (about 18 hours). The catalyst was removed by filtration and carefully washed with ethanol. The combined filtrate and washings were evaporated to dryness in vacuo. The residue was stirred with 80 mL of water for 1 h, filtered, and washed with water to give 3 (14 g) as a white solid. The filtrate and washings were combined and extracted with ether. The combined ether layers were then dried (MgSO4) and concentrated to give an additional 1.3 g of 3 (total yield: 15.3 g, 96%). A small analytical sample was purified by silica gel column chromatography (Rf0.47, CH2Cl2): mp 94-96° C.; 1H NMR (CDCl3) δ4.78 (br s, 2 H, 4-NH2, D2O exchangeable), 6.20 (d, 1 H, 5-H). Analysis calculated for C5H3F3N2: C, 40.55; H, 2.04; N, 18.92. Found: C, 40.60; H, 2.16; N, 18.67.

Provenance & Evidence