Preparation method of 5-ethyl-pyridin-2-ylamine_Industrial additives

Background and overview of the preparation method of 5-ethyl-pyridin-2-ylamine

5-Ethyl-pyridin-2-ylamine is an organic chemical intermediate that can be prepared from 2-amino-5-bromopyridine as a starting material.

Preparation method of 5-ethyl-pyridin-2-ylamine Preparation method

Preparation method of 5-ethyl-pyridin-2-ylamine Method 1.

2-Amino-5-ethylpyridine diethylzinc (24 mL of 1 M in hexane; 24 mmol) was added dropwise to 2-amino-5-bromopyridine (2.0 g, 11.6 mmol) and Pd (dppf M Acyl phenylboronic acid) Cl₂ * CH₂Cl₂ (225 mg, 0.28 mmol) in dioxane (45 mL), nitrogen protection . The mixture was stirred at room temperature for 2 hours, heated to reflux for 3 hours and stirred at room temperature under argon for 70 hours. The mixture was poured into NaCl (aq. saturated solution; 150 mL) and extracted with EtOAc (4 × 100 mL). The combined organic phases were washed with NaCl (saturated, aqueous solution; 100 mL), dried (Na₂SO₄) and concentrated. The residue was purified by chromatography (EtOAc/heptane, then MeOH/EtOAc) to give 5-ethyl-pyridin-2-ylamine. Yield: 1.40 g (99%). ¹H NMR (DMSO-d6, MHz) δ7.74 (s, 1H), 7.25 (dd, 1H), 6.40 (d, 1H), 5.67 (to.s, 2H), 2.39 (q, 2H), 1.10 (t, 3H).

Method 2,

Combine vinyltributyltin (13mL, 44.6mmol), palladium(II) acetate (0.45g, 2.1mmol), triethylamine (12.4mL, 89.1mmol) and tris(o-tolyl)phosphine (3.69g, 12.15 mmol) was added to a solution of 5-bromopyridin-2-amine (7.0 g, 40.5 mmol) in acetonitrile (70 mL), and the reaction mixture was refluxed for 18 hours. The reaction mixture was washed with 2M sodium carbonate solution (80 mL), the organics were separated, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with methanol:dichloromethane 3:97, to obtain 3.6 g of product. The residue was dissolved in dichloromethane and washed with aqueous potassium fluoride solution and then with sodium bicarbonate. The organic solution was dried over magnesium sulfate, filtered and concentrated in vacuo to give 1.9 g of final product.

10% palladium on carbon (300 m g of praseodymium carbonate) was added to a solution of the above amine (1.7 g, 14.1 mmol) in ethanol (80 mL) and the reaction mixture was stirred under 15 psi of hydrogen for 18 h. The reaction mixture was filtered through Arbocel and the filtrate was concentrated in vacuo. The obtained oil was dissolved in dichloromethane, washed with potassium fluoride solution (2 × 10 mL), the organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to obtain 650 mg of product. ¹H NMR (MHz, CDCl₃) δ: 1.16 (t, 3H), 2.48 (q, 2H), 4.35 (br s, 2H), 6.46 (d , 1H), 7.26 (m, 1H), 7.89 (m, 1 H)