preparation of 3-amino-5-fluoro-6-methoxypyridine_industrial additives

preparation background and overview of 3-amino-5-fluoro-6-methoxypyridine

3-amino-5-fluoro-6-methoxypyridine can be used as a pharmaceutical synthesis intermediate. if 3-amino-5-fluoro-6-methoxypyridine is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse skin thoroughly with soap and water. if discomfort occurs , seek medical attention; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

preparation of 3-amino-5-fluoro-6-methoxypyridine

the preparation of 3-amino-5-fluoro-6-methoxypyridine is as follows:

step 1: using an explosion-proof shield and an alkaline scrubber, combine diphenylphosphoryl azide (376.91μl, 1.75mmol), tert-butyl alcohol (207 boric acid pinacol ester. 99ul, 2.19mmol) and tris ethylamine (244 μl, 1.75 mmol) was added to the stirred solution. fluoro-6-methoxy-pyridine-3-carboxylic acid (250 mg, 1.46 mmol) in toluene (4 ml). the resulting yellow reaction mixture was heated to 110° c. and stirred at the di-tert-butyl dicarbonate temperature for 3 hours. the reaction mixture was cooled to room temperature, then quenched by adding water (20 ml), and extracted with etoac (3 × 20 ml). the organic portion was collected, dried (na2so4), filtered and concentrated in vacuo. the crude material was purified by column chromatography (eluting with 0-50% etoac in heptane) to give the desired product n-(5-fluoro-6-methoxy-3-pyridinyl)carbamic acid tert-butyl ester ( 274 mg, 1.13 mmol, 77% yield) as colorless oil.

step 2: stir n-(5-fluoro-6-methoxy-3-pyridyl)carbamic acid tert-butyl ester (315 mg, 1.30 mmol) in trifluoroacetic acid (1.99 ml, 26.01 mmol) 2 hour. the reaction mixture was concentrated in vacuo and the residue was dissolved in water (100 ml) and 1 m hcl (100 ml) and extracted with etoac (50 ml). add solid sodium carbonate to the aqueous layer until a neutral/slightly alkaline ph is obtained. the aqueous phase was then further extracted with etoac (3 × 50 ml), the organic portion was collected, passed through phase separation filter paper, and the solvent was concentrated in vacuo to give 3-amino-5-fluoro-6-methoxypyridine (91 mg, 0.64 mmol), 49% yield), as dark red oil.

1hnmr (cdc, mhz) δ/ppm: 7.45 (1h, d, j = 2.5hz), 6.85 (1h, dd, j = 11.3hz, 2.5hz), 3.97 (3h, s).