邻苯⼆甲酰基保护氨基的脱保护
Pht-氨基衍⽣物很容易⽤肼处理脱去。⼀般⽤⽔合肼的醇溶液回流2 ⼩时或⽤肼的⽔或醇溶液室温放置1-2 天都可完全脱去Pht保护基。在此条件下Cbz、Boc、甲酰基、Trt、Tos等均可不受影响。在肼效果差的情况下，NaBH4/i-PrOH-
H2O(6:1)和AcOH在80℃反应5-8⼩时，这个⽅法是很有效的(见下式)。另外，浓HCl回流也容易脱去Pht保护基。
⼀、 NH2NH2/MeOH脱除邻苯⼆甲酰胺⽰例
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脱除邻苯⼆甲酰胺⽰例
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 ud directly in the next step without further purification.
三、HCl脱除邻苯⼆甲酰胺⽰例
Lee, Chang-Hee;Lee, Jin-Suk et al., J. Org. Chem., 2005, 6, 2067-2074
Compound1(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, withthe 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 ud to the next step without further purification due toits instability.
四、 NaBH4/i-PrOH-H2O(6:1)和AcOH脱除⽰例
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.
