臺灣博碩士論文加值系統

本研究之主題，在合成降血脂藥物,Gemfibrozil： 2,2-dimethyl-5(2,5-
xylyloxy) valeric acid 　　此藥物可經由下列兩種方法合成： (1)以
鈉(NaNH2)取代Me2CHCOPh上的活性氫，再以Br(CH2)3Cl進行烷基化反應，
可得Cl(CH2)3CMe2COPh(b)。將b與無水K2CO3、KI、2,5-xylenol在中度極
性溶劑中迴流數小時，可得2,5Me2C6H3O(CH2)3CMe2COPh(c)。再將c加入
KOCMe3在Anisole中及150℃下反應數小時，可得產物 Gemfibrozil。中間
產物及產物分別以GC-MASS,NMR,IR,EA加以鑑定。總產率約為 15.97%，並
未達到很好的結果，但我們已瞭解部份合成的關鍵。 (2)利用強鹼使
HCMe2COOH形成雙陰離子，再以2,5-Me2C6H3O(CH2)3Cl加以烷基化，可得
Gemfibrozil。此方法，我們只有一次成功的經驗。

2,2-dimethyl-5(2,5-xylyloxy) valeric acid, known as
gemfibrozil, and used for treatment or prevention of
arteriosclerosis, can be produced by these ways: (1)
Abstraction of proton from Me2CHCOPh using NaNH2 followed by
alkylation with Br(CH2)3Cl resulted in Cl(CH2)3CMe2COPh(b).
Refluxing b with anhydrous K2CO3,KI and 2,5-xylenol in a medium
polar solvent gave 2,5-Me2C6H3O(CH2)3CMe2COPh. The latter was
heated with KOCMe3 in anisole to yield gemfibrozil. The results
from GC-MASS, NMR, EA and IR comfirmed the presence of product.
The overall yield was 15.97%. Although the result was not good,
however we have understood some key points about the synthesis.
(2) Abstraction of proton from HCMe2COOR (R is H or alkyl)
followed by alkylation with an alkyl halide, 2,5-Me2C6H3O(CH2)3
Cl, also gave Gemfibrozil。 We only suceededonce by this way.