Application background of 4-benzylpyridine
4-Benzylpyridine is an organic synthesis intermediate and pharmaceutical intermediate that can be used in the laboratory research and development process of methoxyphenylboronic acid and the chemical and pharmaceutical synthesis process. It is a key raw material for the synthesis of ifenprodil tartrate.
Application and preparation of 4-benzylpyridine
A mixture of 4-benzoylpyridine (24, 2.0g, 11mmol), sodium iodide (3.3g, 22mmol) in hydrobromic acid (12ml) and acetic acid (8ml) was heated to mild at 115°C Reflux. Hypophosphorous acid (3.4 ml, 50%, 33 mmol) was slowly added to the reaction via syringe pump over 30 min. The reaction was monitored by TLC and completed within 5 hours. Work-up and removal of solvent gave 1.7 g of a dark red oil. (92% yield). The NMR of the crude reaction product was identical to that of the real sample.
Applications of 4-benzylpyridine
Can be used to prepare ifenprodil tartrate. Ifenprodil Tartrate, also known as benzoperamine tartrate, was first developed by the French company Sanofi-Synthelabo as a cerebral circulation metabolism enhancer. It is a new type of selective NMDA receptor antagonist. It is highly selective and avoids the adverse reactions of non-selective NMDA receptor antagonist drugs, so it has a high degree of safety. Long-term pharmacology, toxicology and clinical trials have proven that it has good therapeutic effect and low toxicity, and is a drug with good market prospects.
Add 3.0g (0.02mol) of 4-hydroxypropiophenone, 8.8g (0.039mol) of copper bromide, 15ml of ethyl acetate, and 15ml of chloroform into the reaction flask, stir, reflux for 3 hours, and then filter to obtain the solid The copper bromide is washed with an appropriate amount of ethyl acetate and recovered; the washing liquid and the filtrate are combined, concentrated to recover part of the solvent, the solution is transferred to a chromatography silica gel column, and quickly filtered using a pressure method to obtain the bromide-containing compound 1-(4-Hydroxyphenyl)-2-bromopropan-1-one is a light brown solution. Concentrate the filtrate to obtain a light brown solid. Add diethyl ether to the solid and stir to dissolve. Petroleum ether was added dropwise to the reaction solution, and a white precipitate gradually precipitated. Continue stirring for 30 minutes and filter. Wash with an appropriate amount of petroleum ether, collect the solid, and dry to obtain 4.6 g of white powder solid 1-(4-hydroxyphenyl)-2-bromopropan-1-one. mp: 94°C to 96°C, HPLC: 99.2%. NMR (DCl3, δppm): CH31.92 (3H, d); CH5.27 (1H, dd); C6H46.92～8.02 (4H).
Add 30 ml of methanol to the obtained solid, stir to dissolve, then add 3.5 ml (0.022 mol) 4-benzylpyridine, stir, and heat to reflux. After 5 hours, stop the reaction and cool to room temperature. HPLC: 94%. The reaction solution does not require additional treatment and can be directly used in subsequent hydrogenation experiments.
Add 50 ml of methanol and 15 g (0.063 mol) of nickel chloride hexahydrate to the reaction solution, and stir to dissolve the solid. Cool the reaction solution to 5-10°C, slowly add 7.5g (0.198mol) of sodium borohydride in batches, complete the addition, and continue stirring for 0.5 hours. Then use 3N HCl to make the reaction solution acidic, concentrate it, and add 150 ml of dilute ammonia and 150 ml of ethyl acetate under freezing. Stir vigorously, filter, and separate the phases. Extract the aqueous phase with ethyl acetate, combine the organic phases, and use anhydrous sodium sulfate. dry. Concentrate and recrystallize tetrahydrofuran with isopropyl alcohol to obtain 4.3g of ifenprodil white solid (containing one molecule of isopropyl alcohol). Yield: 55.8%, mp: 108°C～109°C, HPLC: 99.5%.
