Hydrochloric Acid → 5-(Trifluoromethyl)pyridin-3-amine

2-Chloro-3-nitro-5-(trifluoromethyl)pyridine (0.850 g, 3.75 mmol) was dissolved in methanol (17 mL) and palladium on carbon (800 mg of 10%, 50% wet, 0.375 mmol) was added. The mixture was hydrogenated at 60 psi and 20° C. for 16 h. LCMS showed no remaining starting material or hydroxylamine (M+H 213/215, 3:1) intermediate, and showed a mixture of partially reduced product (M+H 163; UVmax 214, 258, & 332 nm) and the fully reduced product (M+H 169; no UV). The mixture was filtered; and the filtrate was rinsed thoroughly, and concentrated in vacuo to give 0.74 g, of the product as the HCl salt. The product was purified by prep HPLC/MS using a 30 mm×100 mm C18 column; 20% CH3CN—H2O (0.1% NH4OH), 1 min, to 40% at 6 min; 60 mL/min; detector set at m/z 163; retention time, 4.4 min. Fractions containing the pure product were combined and concentrated to give an oil, 52 mg, 8% yield. 1H NMR (CDCl3) δ 8.26 (s, 1H); 8.24 (d, 1H); 7.15 (t, 1H); 4.00 (s, 2H).

1. additiona mixture of partially reduced product (M+H 163; UVmax 214, 258, & 332 nm)
2. filtrationThe mixture was filtered
3. washand the filtrate was rinsed thoroughly
4. concentrationconcentrated in vacuo
5. customto give 0.74 g
6. customThe product was purified by prep HPLC/MS
7. wait20% CH3CN—H2O (0.1% NH4OH), 1 min, to 40% at 6 min
8. customretention time, 4.4 min
9. additionFractions containing the pure product
10. concentrationconcentrated
11. customto give an oil, 52 mg, 8% yield

ORD-Eintrag

ord-678054e7bcd244019686071c0783536f

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08841318B2