Background and overview of preparation and application examples of 5-carboxaldehyde furan-2-boronic acid
5-Carboxaldehyde-furan-2-boronic acid is a boric acid intermediate that is widely used in medicine and other fields. Boric acid compounds can undergo Suzuki reactions with chlorine, bromine or iodinated aromatics and alkenes to connect a variety of groups, and the downstream product polycarbonate diol is very abundant.
Preparation and application examples of 5-carboxaldehyde furan-2-boronic acid
Example report on the preparation and application of 5-carboxaldehyde furan-2-boronic acid 1.
Preparation of 5-carboxaldehyde-2-boronic acid from 2-furancarboxaldehyde-ethylene glycol, triisopropyl borate and sodium powder in THF:
Preliminarily place 1.81g sodium powder (particle size <100μm), 12mg biphenyl and 120g THF in an inertized 250ml Schlenk flask. After stirring at room temperature for 15 minutes, the water is cooled to an internal temperature of 5-10°C and a composition consisting of 14.8 g of triisopropyl borate, 5.1 g of isoprene and 10.5 g of 2-furancarboxaldehyde ethylene glycol is added dropwise within 2 hours. mixture.
After the metered addition has been completed, stir for another 1 hour at approximately 25°C and pour the mixture into approximately 150 g of 15% hydrochloric acid which was stirred and cooled to approximately 0°C using an ice bath.
After, for example, the above-mentioned post-treatment, 260 g of a yellow-light brown solution were obtained, which contained 9.8 g of 5-carboxaldehyde-furan-2-boronic acid according to HPLC analysis. This corresponds to a yield of 93% of theory.
Example report on the preparation and application of 5-carboxaldehyde furan-2-boronic acid 2.
Preparation of 5-formylfuran-2-boronic acid from furfural diethyl acetal and chlorocyclohexane:
The mixture of 20.88g chlorocyclohexane (0.176mol) and 27.2g furfural diethyl acetal (0.16mol) was added dropwise at -65°C to the solution of 2.35g lithium particles (0.34mol) in 300gTHF. In the suspension, the feeding time is selected to be 2 hours. After a conversion of chlorocyclohexane of >97% as determined by GC (total 10 h of tetrahydrofuran), 18.3 g of trimethylborate (0.176 mol) were added dropwise at the same temperature over 30 minutes. After stirring for a further 30 minutes at -65°C, the reaction mixture was poured into 120 g of water, the pH was adjusted to 6.3 with 37% HCl, and THF and cyclohexane were distilled off in vacuo up to 35°C. The pH was then adjusted to 1.5, stirred until complete precipitation of the product, and then filtered off. After washing with some cold water and some cold acetone, and after drying, 17.2 g of 5-carboxaldehydefuran-2-boronic acid (0.123 mol, 77%) was obtained in the form of a beige fine powder with HPLC purity >99% a/a.
Preparation and application examples of 5-carboxaldehyde furan-2-boronic acid
5-carboxaldehyde-furan-2-boronic acid can be used to prepare lapatinib. The method is as follows: under nitrogen protection, combine the compound of formula (IV) with 5-carboxaldehyde-furan-2-boronic acid, organic base or inorganic base, Tetrahydrofuran and ethanol, heat up to 60°C ~ 70°C, stir, add palladium catalyst, temperature-controlled reaction, after the reaction is complete, filter, cool the filtrate, add water dropwise, stir, filter, and dry, the obtained product is further mixed with 2-(methyl sulfone Ethylamine hydrochloride is reacted in the presence of glacial acetic acid, and then NaBH(OAC)3 is added for reduction reaction to obtain lapatinib. The present invention further provides a method for preparing lapatinib di-p-toluenesulfonate, which consists of adding dropwise a tetrahydrofuran solution of p-toluenesulfonic acid monohydrate to lapatinib or its concentrated precursor. This method is simple to operate, uses less solvent, has low production cost, has little environmental pollution, has high product yield and high purity, and is more suitable for industrial production.
References
[1]FromGer.Offen.,102006050717,26Apr2007
[2]CN201510997439.0 Preparation method of lapatinib and its di-p-toluenesulfonate
[3][China invention, China invention authorization] CN02820060.8 Method for preparing organic intermediate products via organometallic compounds
