试验操作To a jacketed vessel with overhead stirring and nitrogen purged was added dichloromethane (1200 mL, 15.0 mL/g) and the solution stirred at 20 °C. To the reactor was added methyl (S)-4-amino-3-(oxetane-2-carboxamido)benzoate 16 (80 g, 1.0 equiv) followed by triethyl borate (164 mL, 3.00 equiv) and 2 M lithium borohydride in THF (200 mL, 1.25 equiv) over 30 min. Upon reaction completion, water (400mL, 5.0 mL/g) was added over no less than 30 min and the resulting mixture was stirred for no less than 2 h before separation of the phases. It was found that reducing the equivalents of LiBH4 from 2.0 to 1.2 and increasing the equivalents of B(OEt)3 from0.75 to 3.0 at 20 °C suppressed impurity formation without compromising reaction conversion. Kinetic studies suggested that the reaction rate decreased substantially once 75% conversion had been reached. This was hypothesized to be due to coordination of the active reducing species to the product, which made reaching full conversion challenging. 参考文献https://doi.org/10.1021/acs.oprd.4c00054
