氯甲酸酯法N-Bn脱苄
氯甲酸酯法是一种高效温和的叔胺N-Bn脱苄方法，尤其对含有易被还原官能团的化合物，此方法是氢化脱苄的很好的互补方法。采用该试剂不会影响分子中的其它官能团。除了苄基还应用于脱去三级胺上的烷基（甲基，乙基等），但其它烷基的反应活性没有脱苄的反应活性高。用于脱苄的氯甲酸酯常见有两个：1-氯乙基氯甲酸酯和2,2,2-三氯乙基氯甲酸酯。1-氯乙基氯甲酸酯脱苄所得氨基甲酸酯在甲醇中加热，即可脱去甲酸酯基得到高收率的仲胺；利用2,2,2-三氯乙基氯甲酸酯脱苄所得到的氨基甲酸酯则需要锌粉还原。
反应机理
机理和von Braun反应类似。
反应实例
【WO2012/42006, 2012, A1】
【US2011/53948, 2011, A1】
To a solution of compound 1 (727 mg) in dichloromethane (75ml) which was being maintained at 0 °C under nitrogen was added 1-chloroethylchloroformate (0.208 ml) dropwise.The mixture was then allowed to warm to room temperature, before being heatedto reflux. After approximately 2 h analysis of the reaction mixture indicatedcomplete consumption of the starting material. The dichloromethane wasevaporated and the residue was then taken up into methyl alcohol and heated toreflux for 1 h. The solvent was evaporated to afford the compound 2 (481 mg, 85%), whichwas used in the next reaction with out further purification.
【US6410592：该方法也可用于脱甲基】
To compound 1 (2.30 g, 6.8 mmol) inacetonitrile (25 mL) was added trichloroethyl chloroformate (0.100 mL, 6.8mmol). The mixture was stirred for 30 min and concentrated. The crude productwas chromatographed (hexanes:methylene chloride = 1:l) to yield compound 2 (2.68 g, 93%) as a white needles, whichcrystallized from absolute ethanol: mp 162.5 °C.
To a solution of compound 2(1.40 g, 3.3 mmol) in acetic acid (30 mL) wasadded powdered zinc (0.5 g) inportions over a period of 2 h. The reaction was filtered, and the precipitate waswashed thoroughly with methylene chloride. The filtrate was concentrated andextracted with ether. The organic layer was neutralized with saturated sodiumbicarbonate solution and dried (Na2SO4). The crudeproduct was concentrated and chromatographed (methylene chloride:ether = 10:1) to yield compound3(0.72 g, 88%) asa yellow oil, which gradually crystallized: mp 103-104°C.
【V. H. Rawal, R. J.Jones et al., J. Org. Chem., 1987, 52, 19】