Boc保护基是有机合成中常遇到的反应。Boc脱除一般在酸性条件下进行，基于Boc对酸的敏感性和对碱的稳定性，碱性和中性脱Boc的案例很少，但是在一些案例当中，酸性条件Boc是脱除不掉的，例如一些吲哚环上的Boc，以及底物对酸性的要求较高的底物，酸性条件不适宜脱除Boc,今天给大家介绍碱性脱除Boc案例。碱性条件：可以是LiOH，NaOH,NaOtBu，溶剂THF等。反应温度可以室温过夜，也可以加热回流。加热会加速反应进程。

2.反应机理

3.合成案例

Sodium t-butoxide (2–4 equiv) was added to a solution of the Boc protected amine (1 equiv) in 2-methyltetrahydrofuran or tetrahydrofuran (10 vol). Volumes is defined as mL of solvent per gram of starting material. Water (1 equiv) was added and the reaction was heated at reflux for 2–12 h. The reaction was cooled to room temperature and quenched with 10% citric acid solution (10 vol). The resulting solution was stirred at room temperature for 30–60 min and then the pH was adjusted to 10–12 with 6 N NaOH solution. The layers were separated. The aqueous layer was further extracted with ethyl acetate (10 vol). The combined organic layers were dried and concentrated to afford the desired amine in 90% to quantitative yield. The crude amine was generally of excellent purity but the crude reaction can be purified by column chromatography or recrystallization if necessary.

室温下，将氢氧化钠(470 mg)加入到化合物9 (350 mg)的甲醇/水= (5 mL/5 mL)混合溶液中、反 应加热到80°C并在该温度下搅拌16小时。反应结束后，在冰浴下将稀盐酸(2M)加入到反应液中调节 pH至7左右，然后直接冻干溶剂，残余物通过高压液相制备色谱纯化(色谱柱：Gemmi-Cl8, 150x21.2 mm, 5 μιη；柱温：25°C；流速：14 mL/min；波长：214 nm;柱压：80bar；流动项：乙腈-水(0.1%甲酸)；梯度：20-40%)得到目标化合物(91.7 mg,收率：32%，含0.6当量的甲酸)。该合成案例当中，吲哚环上酸性条件HC/EA,HCl/dioxane,Boc脱除不了，TFA脱Boc,产物很少，吲哚环上易上三氟乙酰基。反应不好。然而碱性条件不但可以脱除Boc,还可以将酯水解掉，反应干净，无杂质。WO2022028527

参考文献：Tetrahedron Letters  2004, 45, 905–906

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