5-Fluoro-2-pyridinemethanamine

Preparation 85; 2-Aminomethyl-5-fluoropyridine (dihydrochloride); Combine a mixture of 2-cyano-5-fluoropyridine (63.2 g, 0.52 mol), 22.5 g of Raney nickel, and ethanol (1.5 L) saturated with ammonia and hydrogenate at 500 p. s. i. and 70 ° C for 16 h. Chromatograph the dark purple liquid over flash silica gel (methylene chloride/methanol/ammonia hydroxide-95: 4.5 : 0.5) to give, after concentration at 25-30 ° C, a yellow liquid of the pure desired free base, 25.0 g (44percent); 'H NMR (DMSO-d6) 8 8.43 (d, J= 2.9 Hz, 1H), 7.66 (m, 1H), 7.50 (m, 1H), 3.77 (s, 2H), 2.10 (br, 2H); MS (ESI) m/z 127 (m+H). Add to a solution of the free base (20.0 g, 159.0 mmol) in 150 ml of 1, 4-dioxane, 4N HC1 in dioxane (150 mL, 3.8 eq. ) and a white solid separates immediately. Dilute the solid with ethyl ether (300 mL) and filter. Dry the product at 20 mm Hg, 60 ° C, to give the pure dihydrochloride title compound, 30.0 g (95percent) ; lH NMR (DMSO-d6) 6 8.61 (d, J= 2.9 Hz, 1H), 8.50 (brs, 3H), 7.82 (m, 1H), 7.62 (m, 1H), 7.50 (br, 1H), 4.18 (m, 2H); MS (ESI) m/z 127 (rn+H, free base).To a solution of 5-fluoropicolinaldehyde oxime (333 mg, 2.38 mmol) and nickel chloride (308 mg, 2.38 mmol) in anhydrous ethanol (18 mL) was added sodium borohydride (476 mg, 11.88 mmol) under an ice-bath condition accompanying intense heat, then the mixture was stirred for additional 40 minutes under the ice-bath condition. The mixture was stirred at rt for 20 minutes, then hydrochloric acid solution was added to adjust the pH to about 1. The resutling mixture was stirred until clear, then sodium hydroxide was added to adjust the pH to about 14 and a white solid was precipitated. The upper layer of the suspension was seperated and the solvent of the upper layer was removed. To the residue was added dichoromethane (25 mL) , and the mixture was filtered. The filtrate was dried over anhydrous sodium sulfate and concentrated to give a light yellow solid (150 mg, 50) .[2025]

Molecular Weight:126.13
XLogP3:-0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:126.05932639
Monoisotopic Mass:126.05932639
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:87.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes