2-Amino-4-(trifluoromethyl)pyridine

Preparation of 2-amino-4-(trifluoromethyl)pyridine from 5-ethoxy-3-hydroxy-3-(trifluoromethyl)pent-4-enenitrile with Aqueous Ammonia; 50 g of 5-ethoxy-3-hydroxy-3-(trifluoromethyl)pent-4-enenitrile were mixed with 600 g of aqueous ammonia (25percent), and the resulting mixture was heated to 125° C. in an autoclave for 24 h, in the course of which a pressure of approx. 14 bar built up. Subsequently, the reaction mixture was cooled and the resulting biphasic mixture was extracted repeatedly with dichloromethane. The combined organic phases were cautiously concentrated by rotary evaporation, and the product was subsequently recrystallized from cyclohexane. 26.3 g of 2-amino-4-(trifluoromethyl)pyridine (68percent) were thus obtained as a yellowish-brown solid. The spectroscopic data agreed with those reported in the literature (A. D. Dunn et al. in J. Fluorine Chem. 1999, 93, 153-157), Example 5 In an autoclave (200 mL), 10 g (0.046 moles) of 2, 6, 4-DCTF, 30.6 mL (0.44 moles) of 28 percent ammonia water, and 20 mL of THF were heated to 150 °C with stirring to effect reaction. After about 6 hours, the autoclave was cooled to from 30 to 40 °C, 300 mg of 5 percent Pd/C (54 percent wet, 0.076 mmoles) was added thereto, hydrogen was filled up to 2.0 MPa, followed by heating to 100 °C with stirring to effect reaction. After about 3 hours, the pressure reactor was cooled to from 30 to 40 °C, followed by filtration through Celite. Water was added to the filtrate; the extraction with ethyl acetate was conducted three times; and an organic layer was washed with saturated saline and then dried over sodium sulfate. The organic layer was concentrated under reduced pressure, and n-hexane was added, followed by concentration. To a deposited crystal, n-hexane was added, followed by stirring under ice cooling for about 60 minutes, and a deposited crystal was filtered. The obtained crystal was subjected to washing with ice-cooled n-hexane three times and then dried under reduced pressure to obtain 5.4 g of 2, 4-ATF as a white crystal (yield: 71.9 percent, melting point: 70.1 °C). In addition, an NMR spectrum data of the obtained crystal is as follows.

Molecular Weight:162.11
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Exact Mass:162.04048265
Monoisotopic Mass:162.04048265
Topological Polar Surface Area:38.9
Heavy Atom Count:11
Complexity:134
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes