Methyl cis-3-hydroxycyclobutanecarboxylate synthesis

Yield:63485-50-7 88%

Reaction Conditions:

with lithium tri-t-butoxyaluminum hydride in tetrahydrofuran at -78 - -60; for 4 h;Large scale;Reagent/catalyst;

Steps:

1 Example 1 Preparation of cis-3-hydroxycyclobutylcarboxylic acid methyl ester
3-oxocyclobutanecarboxylic acid methyl ester (3075 g, 24.0 mol, 1.0 eq.) was dissolved in 30 L of tetrahydrofuran and cooled to -78 to -60 ° C.20 L of a solution of lithium tri-tert-butoxyaluminum hydride (9154 g, 36.0 mol, 1.5 eq.) in tetrahydrofuran was added dropwise, and the reaction was kept for 4 h.After completion of the TLC test, the reaction was quenched by dropwise addition of 6 mol L-1 hydrochloric acid, the pH of the reaction solution was adjusted to be between 5 and 6, and the temperature was controlled at about 0 ° C, diluted with 20 L of ethyl acetate and stirred for 30 min.The pad was filtered through celite, and the filter cake was washed three times with ethyl acetate, and the filtrate was separated.The aqueous phase was extracted with ethyl acetate and washed All organics were combined, dried and concentrated to give a pale yellow liquid of cis-3-hydroxycyclobutylcarboxylic acid methyl ester (2733g, 21.0mol), yield 88%, purity 95%.

References:

Shanghai Bide Pharmaceutical Technology Co., Ltd.;Xiong Shichuan;Mi Taoran;Fan Jianjian;Zhang Ruihao CN108129288, 2018, A Location in patent:Paragraph 0047; 0048; 0052

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