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Debenzylation of 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-benzyloxyphenyl)-2-azetidinone to 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone Disclosure Number: IPCOM000126460D
Publication Date: 2005-Jul-19
Document File: 2 page(s) / 80K

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The Prior Art Database

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Debenzylation of 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)- hydroxypropyl]-4(S)-(4-benzyloxyphenyl)-2-azetidinone to 1-(4- fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)- (4-hydroxyphenyl)-2-azetidinone

    1-(4-fluorophenyl)-3-(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4- hydroxyphenyl)-2-azetidinone (referred to as EZT) belongs to a class of lipid- lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols.

EZT reportedly does not inhibit cholesterol synthesis in the liver or increase bile acid excretion. Instead, it appears that 1-(4-fluorophenyl)-3-(R)-[3-(4-fluorophenyl)-3(S)- hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone localizes and acts at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. The result is a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood.

EZT having the following chemical structure

may be obtained, for example, by debenzylation of 1-(4-fluorophenyl)-3(R)-[3-(4- fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-benzyloxyphenyl)-2-azetidinone (referred to as BZT).

    BZT may be obtained, for example, according to the methods provided in US patent No. 5,631,365.

    The debnzylation process of BZT comprises the steps of: combining BZT, with iso-propanol or with a mixture of iso-propanol and water, and heating, preferably


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to reflux temperature, to obtain a solution. Preferably, the mixture cont...