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 reaction 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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