MOM(甲氧基甲基醚)保护羟基

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MOM(甲氧基甲基醚)是一种保护羟基的常用方法;其对酸还是较为稳定的,一般它的脱除需要在强酸条件下进行。


保护条件:

CH3OCH2Cl(MOMCl),DIEA,在二氯甲烷中,0℃到室温,反应8h,在引入MOM时,此条件是最常用的方法。但是MOMCl是致癌物,而且在制备MOMCl时产生的二氯甲基甲基醚毒性更强。因此在使用MOMCl时要做好防护措施。


MOM(CH3OCH2-OR)羟基保护示例(J. Org. Chem. 1995,60,7796)


To a stirred solution of (1) (51.0 g, 99 mmol) in CH2Cl2(1.0 L) at room temperature were successively added DIEA (51.5 mL, 0.297 mol) and MOMCl (15.0mL, 0.198 mol) over a 10 min period.  Thesolution was stirred 11 h at room temperature after which a saturated aqueousNH4Cl solution (200 mL) was added. The aqueous phase was segregated, and the organic one was washed withwater (100 mL), brine (100 mL0, dried with anhydrous MgSO4, filtered, andconcentrated to give pure MOM ether (2) (55.3 g, 100%) (slightly yellowish oil).

二、利用MOMCl上保护时,对于位阻较大的羟基,有时在反应中会加入NaI促进反应。原位生成了MOMI增加了反应活性。

三、CH2(OMe)2,DCM,TfOH,室温4h,产率65%。【J. Org. Chem., 57, 940(1992)】此方法使用于生成伯、仲、烯丙基和炔丙基的MOM醚。叔醇不能完全反应,1,3-二醇则生成亚甲基缩醛。

利用甲醛二甲缩醛上MOM的方法中,还有其他酸性催化的方法,如TsOH/LiBr,无水三氯化铁,五氧化二磷等等。


脱保护条件:

一、少量浓盐酸,甲醇,62℃,15min。

二、6M HCl, THF/H2O,50℃,5-8h。

三、少量浓盐酸,异丙醇,加热。


To a stirred solution (1) (1.00 g, 1.45 mmol) in dry isopropylalcohol (10.0 mL) were added two drops (~0.06 mL) of concentrated aqueous hydrochloric acid.  The solution was stirred at 55oC for 10 h and although incomplete as indicated by TLC analysis, was allowed to cool to room temperature (prolonged reaction timestend to give substantial decomposition). A saturated aqueous NaHCO3 (20 mL) and diethyl ether (50 mL)were added to the mixture.  The phase wasseparated and the aqueous layer was extracted with diethyl ether (5 ´ 50 mL).  The combined organic layer was washed with brine (10 mL), dried over MgSO4, filtered, and concentrated.  The crude product was purified by flashchromatography to give (2) (0.63 g, 65%).


四、苯硫酚,三氟化硼乙醚,98%产率。【J. Am. Chem. Soc., 100,1938(1978)】

五、PPTS(对甲苯磺酸吡啶盐),叔丁醇,回流80-90%产率。【Synth. Commun., 13, 1021(1983)】


六、三氟乙酸,二氯甲烷,产率85%。【J. Am. Chem. Soc.103,3210(1981)】

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