2,4-二甲氧基苄基（DMB）是较稳定的胺基保护基之一,对催化氢解较Cbz、PMB和Bn稳定，故用H2/8%Pd-C/EtOH处理，则可除去Bn，而保留N-DMB。同样，用Pd(PPh3)4/HOAc/THF处理，则可保留N-DMB, 而除去Alloc。酰胺的苄基，常规加氢方法不易脱除，但DMB和PMB容易脱除。在设计合成路线时，2,4-二甲氧基苄胺常被用为氨的等价物加以使用。

2,4-二甲氧基苄基（DMB）引入

2,4-二甲氧基苄基（DMB）一般由ArCHO/NaBH3CN或NaBH(OAc)3还原胺化引入。

Moore, M. Caragh; Cox, Russell J et al., Tetrahedron, 1998, 54(31), 9195-9206

Methanolic HCl was added toa stirred solution of L-phenylalanine methyl ester (4.33 g，24.16 mmol) in methanol (100 mL) to adjust to pH 6.2,4-Dimethoxybenzaldehyde (4.82,  29.00 mmol)was then added, the solution stirred at 20°C for 30 min and then NaBH3CN (2.20 g，35.01mmol) was added and the reaction stirred for afurther 16h. The solvent wasremoved in vucuo, water (50 mL) added and the solution extracted with diethyl ether(3x 100 mL). The organic extractswere combined: washed with an aqueous solution of FeSO4, dried (MgSO4), filtered and reduced in vucuo,to afford a crude pruduct as a pale yellow oil. Impurities of2,4-dimethoxybenzylalcohol were removed by distillation under reduced presure(furnace temparature 110°C,0.1 mmHg). The product could be further purified by chromatography (hexane:ethylacetate, 50 : 50) to give compound 1 (3.71 g, 11.26 mmo1, 46.6%) [α]21D= - 65.22 (c = 0.01, EtOH). 

2,4-二甲氧基苄基（DMB）脱去

DMB容易用酸脱去，如用TFA, TosOH或HCl的有机溶液在0℃或室温即可顺利除去。采用TFA/i-Pr3SiH/CH2Cl2时,N-Fmoc可以稳定不动。其他如DDQ/CH2Cl2也能很方便的脱去DMB，而叔丁酯和N-Boc可以不受影响。

一、2,4-二甲氧基苄基（DMB）酸脱去示例

Hill, Bryan; Liu, Yong et al., Org.Lett.,2004, 6(23), 4285-4288

Route A: To a cooled 0°C solution of Sulfonamide 3 (43.5 mg, 0.117 mmole) and CH2Cl2 (2.6 mL)wasadded TFA (1.1 mL). The reaction mixture immediately turned pink. The reactionwas stirred at 0°Cfor 4.5 hrs then the solvent was removed in vacou to yield a pink solid. The solid was suspended in acetone and filteredthru a plug of cotton (acetone rinse). The filtrate was evaporated and theresidue purified by flash chromatography (15:85 EtOAc:Hexanes) yieldedsulfonamide 2 (23.4 mg, 90%) as a clear colorless oil.

Route B: A solution of sulfonamide 1 (96.2 mg, 0.286 mmole), 1N HCl (3.8 mL) and THF (3.8 mL)was stirred at rt overnight. The mixture was diluted with Et2O, washed with aq. NaHCO3, brine, dried over MgSO4, filtered and concentrated. Flashchromatography (15:85 EtOAc:Hexanes) yielded sulfonamide 2 (55.2 mg,87%).

二、DDQ脱去2,4-二甲氧基苄基（DMB）示例

Dagoneau,Christelle; Denis, Jean-Noeel et al., Syn.Lett., 1999, 5, 602-604

A solution of ester 1(0.08mmol) andDDQ (0.28mmol) in CH2Cl2/H2O (19/1, 6mL) was stirred for 1 day at r.t. The mixturewas then diluted with CH2Cl2and treated bya saturated aqueous solution of NaHCO3. Classical work-up, followed bycolumn chromatography (silica gel, AcOEt/pentane:1/9) afforded the N-Bocamine 2 as a colorless oil. 

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