Processing method of lactionization in the preparation of statins
The present invention relates to a processing method for preparing lovastatin and simvastatin which comprises the steps of (1) performing lactonization of mevinic acid and its homologous compounds in the presence of a mixed organic solvent without an acid catalyst through nitrogen sweep; and (2) making crystals. In the process of the present invention, lovastatin and simvastatin highly purified can be produced in a high yield and especially, heterodimers formed as a by-product can be reduced remarkably. Therefore, the processing method of the present invention can be convenient and economical.
1. A processing method for preparing a compound of formula 1 which comprises the steps of(1) performing lactonization of a compound of formula 2 in the presence of a mixed organic solvent without a catalyst through nitrogen sweep; and (2) making lactone product into crystal;
wherein Z is hydrogen, ammonium or metal cation, R is a radical of formular 3 and R 1 is H or CH 3 .
2. The processing method for preparing the compound according to claim 1 , wherein said mixed organic solvent can be a mixture of more than two selected from a group consisting of toluene, ethyl acetate, isopropyl acetate, dichloromethane, chloroform, tetrahydrofuran and acetone.
3. The processing method for preparing the compound according to claim 1 , wherein said mixed organic solvent is a mixture of toluene and acetonitrile, or dichloromethane and acetonitrile.
4. The processing method for preparing the compound according to any one of claims 1 to 3 , wherein said mixed organic solvent is utilized in 40 part by weight against 1 part by weight of the compound of formula 2.
5. The processing method for preparing the compound according to claim 1 , wherein said step of making lactone product into crystal utilize more than one solvent selected from a group consisting of water, ethanol, isopropyl alcohol, n-hexane, cyclohexane, toluene, ethyl acetate, isopropyl acetate, acetonitrile, acetone, dichloroethane and chloroform.
6. The processing method for preparing the compound according to claim 5 , wherein said solvent is a mixed solvent comprising 8 to 10 part by weight of water and 8 to 10 part by weight of ethanol, or a mixed solvent comprising 2 to 3 part by weight of toluene and 19 to 21 part by weight of cyclohexane against 1 part by weight of the compound of formula 2.