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      对甲氧基苄基（PMB）是也最稳定的氨基保护基之一。它对大多数反应都是稳定的，在Bn存在下，可用CAN或DDQ氧化选择脱PMB；同样，在Boc和叔丁酯存在下，可用CAN氧化选择脱PMB；也可用H2/Pd(OH)2去掉Bn，而保留PMB。

对甲氧基苄基（PMB）的引入

PMB一般采用MeOC6H4CH2Br或MeOC6H4CH2Cl和碱（K2CO3、DIPEA、NaH和DBU等）在有机溶剂(如DMF、二氯甲烷和乙腈等)中反应来引入，或MeC6H4CHO/NaBH3CN或NaBH(OAc)3还原胺化等。

一、烷基化引入对甲氧基苄基（PMB）

J. Cossy; I. Pevet et al., Eur.J. Org. Chem., 2001, 15, 2841

Anhydrous K2CO3(780 mg, 5.66 mmol, 2.0 equiv.), n-Bu4NI (100 mg,0.28 mmol, 0.1 equiv.), and p-methoxybenzyl bromide (630 mg, 3.11 mmol,1.1 equiv.) were added successively to a solution of compound 1(700 mg, 2.83 mmol) in CH3CN (6 mL).After 1 h at 40°C and overnight at room temperature,the mixture was diluted with ether, filtered, and concentrated under reducedpressure. The crude material was purified by flash chromatography (cyclohexane-AcOEt,95:5 to 90:10) to give 0.68 g(65%) of compound 2 as colorless oil. [α]D20 = +12.5 (c = 2.02, CHCl3).

 

 

二、烷基化引入对甲氧基苄基（PMB）示例2

R. Caputo; C.Romualdo et al., Eur. J. Org. Chem., 2002, 17, 3050

A magnetically stirred suspensionof compound 1 (0.39 g;2.84 mmol) and diisopropylethylamine (DIPEA, 25 mL; 0.14 mmol) in toluene (10mL) was gently warmed until a clear solution was obtained. 4-Methoxybenzyl chloride(2.3 mL; 17 mmol) was then added in one portion, and the resulting solution washeated under reflux, and also the intermediate N-monosubstitutedderivative were completely consumed (ca. 5 h, TLC monitoring). The reactionmixture was then cooled in an ice bath, diluted with ethyl acetate (0.2 L), and extracted with 10% aq. NH4Cl. The organiclayer was washed with brine and dried (Na2SO4), and the solvents wereevaporated under reduced pressure to afford a crude reaction product,chromatography of which on silica gel (petroleum ether/Et2O, 8:2) gavethe pure, oily title compound 2 (0.37 g; 85%).

 

三、还原胺化引入对甲氧基苄基（PMB）示例

 

P. Wipf; C. R. Hopkins et al., J. Org. Chem., 2001, 66(9), 3133

To a solution of 5.031 g (11.17 mmol) of amine 1 in 13 mL of MeOH was added at 0 °C 712.7 mg (11.34 mmol) of NaBH3CN followed by1.50 mL (1.68 g, 12.3mmol) of p-anisaldehyde and 0.5 mL of AcOH. The reaction mixture waswarmed to room temperature, stirred overnight, and quenched with H2O and solid Na2CO3. The viscoussuspension was transferred to a separatory funnel and extracted with CH2Cl2. The combined organicextracts were dried (Na2SO4) and concentrated in vacuo to give a bright yellow oilthat was purified by chromatography on SiO2(hexanes/EtOAc; 9:1) to afford 5.324 g (9.336 mmol, 84%) of amine 2 as a lightyellow oil: [α]D = -37.3 (c = 0.74, CHCl3).

对甲氧基苄基（PMB）的脱去

对甲氧基苄基（PMB）的脱去较多，除了常规的催化氢解外，CAN、 DDQ或SmI2氧化去保护和在TFA中加热脱去也经常应用。

一、 DDQ脱去对甲氧基苄基（PMB）示例

S. D. Bull; S. G. Davies et al., J.Chem. Soc. Perkin Trans. 1, 2000, 22(1), 3765-3774

DDQ (1.15 g, 2.1 mmol) was added portionwise to a stirredsolution of compound 1 (400mg, 1.0 mmol) in MeCN-H2O (5 : 1, 6 mL) and stirred at RT. The reaction wasquenched by the addition of saturated aqueous sodium bicarbonate solution andstirred vigorously for ten minutes before extracting with Et2O. The combinedorganic extracts were dried (MgSO4), filtered andconcentrated in vacuo efore purification by column chromatography on silica gel (hexane-Et2O 2: 1) to givecompound 2 (246 mg, 79%)as a colourless oil.

 

二、CAN脱去对甲氧基苄基（PMB）示例

P. P. Obrien; W.David et al., Syn. Lett., 2000, 9, 1336

A mixture of compound 1 (104mg, 0.2 mmol) and CAN (350 mg, 0.6 mmol) in a 1:1 solution of MeCN-water (0.86 mL)was stirred at 0 °C for 30min. Brine (5 mL) was added and the mixture extracted with EtOAc (3 x10 mL).The combined organic extracts were dried (MgSO4) and evaporated under reducedpressure. Purification by chromatography on silica with petrol-EtOAc (6:1) aseluent gave amine 2 (65 mg, 87%) as a yellow oil.

 

三、TFA脱去酰胺对甲氧基苄基（PMB）示例

S. F. Martin; G.O. Dorsey et al., J. Med. Chem., 1998, 41(10), 1581

Compound 1 (200 mg, 0.810 mmol)was dissolved in trifluoroacetic acid (TFA) (10 mL), and the solution wasstirred for 24 h at room temperature. The reaction mixture was concentratedunder reduced pressure, and the residue was dissolved in CH2Cl2(50 mL). The organic layer

was washed with water (2 x25 mL), dried (MgSO4), and concentrated under reduced pressure to leave awhite solid that was purified by flash chromatography eluting with hexanes/EtOAc(1:1) containing 2% AcOH to give compound 2(180 mg, 77%) of as a white solid: mp 150-152 °C.

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