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US 9,040,698 B2Granted
Method for preparing optically pure (+)-ambrisentan and (+)-darusentan
AssigneeInstitute of Chemistry, Chinese Academy of Sciences
InventorsYian Shi, Xianyou Peng, Peijun Li
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Abstract
Disclosed is a method for preparing optically pure (+)-ambrisentan and (+)-darusentan, comprising: firstly catalyzing the asymmetric epoxidation of a β-unsaturated alkene using a chiral ketone derived from fructose or a hydrate thereof as a catalyst, and then subjecting the product to an epoxy compound ring-opening reaction and substitution reaction successively to obtain optically pure (+)-ambrisentan and (+)-darusentan.
Claims9
A method for preparing a compound represented by formula (I), including the steps:
- (1) in the presence of a catalyst and an oxidant, conducting an epoxidation reaction of 3,3-diphenyl acrylate represented by formula (II) to obtain (2S)-epoxy-3,3-diphenyl acrylate represented by formula (III);
- said catalyst is a chiral ketone derived from fructose represented by formula (IV) or a hydrate thereof represented by formula (V), and characterized in that the oxidant is selected from any one of sodium perbromate, sodium periodate, potassium monopersulfate, potassium peroxymonosulfate and hydrogen peroxide,
- wherein, Ph is phenyl;
- Ac is acetyl;
- R1 is selected from any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclohexyl and benzyl;
- R is one of methyl and methoxy;
- (2) in the presence of an acidic catalyst and methanol, conducting an epoxy ring-opening reaction of (2S)-epoxy-3,3-diphenyl acrylate represented by formula (III) to obtain (2S)-2-hydroxyl-3-methoxy-3,3-diphenyl acrylate represented by formula (VI);
- wherein, Ph is phenyl;
- Ac is acetyl;
- R1 is selected from any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclohexyl and benzyl;
- (3) in the presence of an alkaline compound, conducting a nucleophilic substitution reaction of (2S)-2-hydroxyl-3-methoxy-3,3-diphenylacrylate represented by formula (VI) and methylsulfonyl pyrimidine represented by formula (VII) to obtain a compound represented by formula (VIII);
- wherein, R is one of methyl and methoxy;
- R1 is selected from any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclohexyl and benzyl;
- (4) in the presence of an alkaline compound, conducting a hydrolysis reaction of the compound represented by formula (VIII), then acidifying by a protonic acid, thereby obtaining the compound represented by formula (I).
11 more elements
Dependencies are inferred from the claim text.