氯甲酸酯法N-Bn脫芐

氯甲酸酯法是一種高效溫和的叔胺N-Bn脫芐方法，尤其對(duì)含有易被還原官能團(tuán)的化合物，此方法是氫化脫芐的很好的互補(bǔ)方法。采用該試劑不會(huì)影響分子中的其它官能團(tuán)。除了芐基還應(yīng)用于脫去三級(jí)胺上的烷基（甲基，乙基等），但其它烷基的反應(yīng)活性沒有脫芐的反應(yīng)活性高。用于脫芐的氯甲酸酯常見有兩個(gè)：1-氯乙基氯甲酸酯和2,2,2-三氯乙基氯甲酸酯。1-氯乙基氯甲酸酯脫芐所得氨基甲酸酯在甲醇中加熱，即可脫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脫芐所得到的氨基甲酸酯則需要鋅粉還原。

利用芐基保護(hù)胺基不是一個(gè)很好的方法，很多時(shí)候不好脫掉。

反應(yīng)機(jī)理

機(jī)理和類似。

反應(yīng)實(shí)例

【W(wǎng)O2012/42006, 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：該方法也可用于脫甲基】

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】