Preparation and application of 2-pyridyl acetic acid_Industrial additives

Background and overview of the preparation and application of 2-pyridylacetic acid

2-Pyridyl acetic acid can be used as a pharmaceutical synthesis intermediate. If 2-pyridyl acetic acid is inhaled, move the patient to fresh air; if the skin comes in contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical treatment if you feel uncomfortable; if the eyes come into contact, seek medical attention. 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 and application of 2-pyridyl acetic acid

The preparation of 2-pyridylacetic acid is as follows:

The specific steps are: “Add KOH aqueous solution (13 mL) (2.04g, 36.32 mmol, 1.2 equivalent) to EtOH solution (40 mL) of ethyl 2-pyridyl acetate (5.00 g, 30.27 mmol, 1 equivalent). The resulting solution was stirred at 50 °C (2 h). The solution was concentrated to one-third of the original volume of ammonium bicarbonate and washed with Et2O (3 × 20 mL). The aqueous layer was washed with concentrated aqueous HCl (3.0 mL). and, then concentrated in vacuo. Crude 2-(pyridin-2-yl)acetic acid (4.15 g) was used in the next step without further purification: Rf = 0.06 (EtOAc); 1H NMR (DMSO-d6) δ 3.93 (s, CH2), 7.54 (dd, J=1.8, 5.4Hz, H4), 7.60 (d, J=7.9Hz, H6), 8.06 (dt, J=1.8, 7.9Hz, H5), 8.64 (d, J=5.4 Hz, H3).

Preparation and application of 2-pyridyl acetic acid

2-Pyridyl acetic acid can be used as a pharmaceutical synthesis intermediate. If the following reaction occurs:

The specific steps are: add (4-(3-fluorobenzyloxy)phenyl)methyl to a CH3CN solution (20mL) of 2-pyridylacetic acid (1.48g, 10.81mmol, 1 equivalent) at 0°C. Indium amine fluoroborate (2.50 g, 10.81 mmol, 1 equivalent). After adding DMF (5 mL), the reaction contents went into solution, then TBTU (4.16 g, 12.97 mmol, 1.2 equiv) was added at 0 °C. The reaction mixture was stirred at room temperature under Ar (16 h)). The reaction mixture was concentrated in vacuo. EtOAc (50 mL) was added, the organic layer was washed with H2O (5 × 50 mL), brine (2 × 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was purified by flash liquid chromatography on silica gel using EtOAc/hexane (5/5 to 10/0) ​​as eluent. The white solid was recrystallized from EtOH to give N-4-(3-fluorobenzyloxy)benzyl-2-(pyridin-2-yl)acetamide as a white solid (1.48g, 39%): Rf 0.43 ( EtOAc); melting point 127-129°C.