Background and overview of the preparation method of 1-tert-butoxycarbonyl-2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester
1-tert-butoxycarbonyl-2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester is a borate ester compound. In scientific research, boronic acid ester compounds are mainly used as a type of synthetic intermediates, used in transition metal-catalyzed cross-coupling reactions to construct target compounds with complex structures. In industrial production, borate ester compounds are widely used in the fields of medicine, pesticides and materials.
Preparation method of 1-tert-butoxycarbonyl-2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester
Add 3-oxopyrrolidine-1-carboxylic acid tert-butyl ester (20.0g, 0.11mol, 1.0 equivalent) and THF (200mL) into a flask dried under N2. The solution was cooled in an acetone ice bath (-78°C). To this was added LiHMDs (125 mL, 0.12 mol, 1.15 equiv) (1M solution in THF). The reaction mixture was stirred at -78°C for 30 min, and then 1,1,1-trifluoro-N-phenyl-N-((trifluoromethyl)sulfonyl)methanesulfonamide (46.3g, 0.13mol, 1.2 equiv) in THF (200 mL). Barium metaborate The reaction mixture was stirred for 30 min, then heated to 0°C and stirred for 1.5 h. The reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated. The crude product was purified by column chromatography (PE/EA=30/1, v/v) to obtain 3-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1H-pyrrole -1-tert-Butylcarboxylate (20.5g, 59.8%).
Dissolve 3-trifluoromethanesulfonyloxy-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester (21.0g, 66.2mmol, 1.0 equivalent) in 1,4-dioxane alkane (300 mL), and add the above calcium carbonate solution to potassium acetate (19.5g, 200.0mmol, 3.0 equivalent), Pd(dppf)Cl2·CH2Cl2 (2.7g, 3.3mmol, 0.05 equivalent), DPPF ( 1.84 g, 3.3 mmol, 0.05 equiv) and bis(pinacol)diborane (20.0 g, 79.5 mmol, 1.2 equiv), and the reaction mixture was heated at 90°C overnight. The crude reaction mixture was concentrated and purified by flash column chromatography (PE/EA=10/1, v/v) to obtain 1-tert-butoxycarbonyl-2,5-dihydro-1H-pyrrole-3-boronic acid pinacol Alcohol ester (11.4g, 58.3%).
References
[1] [Invented in China] CN201780063561.8 Certain chemical entities, compositions and methods
