Pht-氨基衍生物很容易用肼處理脫去。一般用水合肼的醇溶液回流2 小時或用肼的水或醇溶液室溫放置1-2 天都可完全脫去Pht保護基。在此條件下Cbz、Boc、甲?；?/span>Trt、Tos等均可不受影響。在肼效果差的情況下，NaBH4/i-PrOH-H2O(6:1)和AcOH在80℃反應5-8小時，這個方法是很有效的(見下式)。另外，濃HCl回流也容易脫去Pht保護基。
一、 NH2NH2/MeOH脫除鄰苯二甲酰胺示例
W. Shijun; Y.Zhujun et al., Org. Lett., 2004, 16, 2721
To a solution of compound1 (313 mg, 1.04 mmol) in MeOH (6 mL) was added hydrazinemonohydrate (0.1 mL, 1.67 mmol) at 0 °C.After being stirred at same temperature for 3h, the solvents were removed invacuo and the residue was re-dissolved into water (10 mL). The pH ofsolution was then adjusted to 1-2 by adding 1N HCl at 0 °C.The whole mixture was stirred for 1 h at rt, and then filtered. The filtratewas treated with solid Na2CO3untilthe pH reached 9-10. The mixture was extracted with CH2Cl2(10 mL x 4). Thecombined extracts were dried (Na2SO4), concentrated and dried in vacuo toprovide compound 2 (209mg, quantitatively) as a yellowish oil.
二、NH2NH2/EtOH脫除鄰苯二甲酰胺示例
Lee, Chang-Hee;Lee, Jin-Suk et al., J. Org. Chem., 2005, 6, 2067-2074
Compound 1 (1.66 g, 4.77 mmol) was dissolved in ethanol(50 mL), and then hydrazine monohydrate (0.93 mL, 19 mmol) was added. Theresulting mixture was heated at reflux for 24 h and then cooled to roomtemperature. The mixture then was combined with aqueous NaOH (50 mL) andextracted with CH2Cl2. The solvent was removed in vacuoto afford compound 2 (0.79 g,76%), which was used directly in the next step without further purification.
三、HCl脫除鄰苯二甲酰胺示例
Lee, Chang-Hee;Lee, Jin-Suk et al., J. Org. Chem., 2005, 6, 2067-2074
Compound 1 (1.0 g, 3.86 mmol) and concentrated HCl (3 mL)was heated for 60 h at 100 °C.After the mixture was allowed to cool to room temperature, water (20 mL) wasadded. The solid precipitate that formed was removed by filtration anddiscarded, and the aqueous layer was washed with diethyl ether twice, withthese washings also being discarded. The water was removed in vacuo, and the remainingsolid was dried to give compound 2 (0.61 g,95%), which was then used to the next step without further purification due toits instability.
四、 NaBH4/i-PrOH-H2O(6:1)和AcOH脫除示例
J. O. Osby; M. G. Martin et al., Tetrahedron Lett., 1984,25, 2093-2096
To a stirred solution ofcompound 1 (0.36 g, 1mmol) in 2-propanol (7.7 ml) and H2O (1.3 ml) was added NaBH4(0.19 g, 5 mmol). After stirring24 h, TLC indicated complete consumption of starting material. AcOH (1 ml) wasadded carefully and when the foaming subsided, the flask was stoppered andheated to 80°C for2 h. The crude reaction mixture was then eluted onto a Dowex 50 (H+)column (2.7 x 10 cm),washed with H2O (150 ml), then eluted with 1 M NH4OH (200 ml). Ninhydrin-active fractions werecollected and pooled for freeze drying, and thus afforded compound 2 (0.2 g, 89%) as an ammonium salt.
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