Process for producing a purified prostaglandin derivative
AssigneeMitsubishi Pharma Corporation
InventorsMasahiro Urushihara, Yoshitomi Morizawa
Life of this patent
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Abstract
An alkene (1) is added to cyclopentenone (2) under the action of an alkyl lithium and an organic copper reagent to form an adduct, said adduct is reacted with e.g. a carboxylic anhydride (4) to obtain a prostaglandin derivative (6), which is then treated with a nitrogen-containing compound such as 2,2′-bipyridyl to efficiently remove the organic copper reagent used in the synthesis and by-products derived from said reagent, to obtain a purified prostaglandin derivative (6) having a high purity:
Claims23
A process for producing a purified prostaglandin derivative, which comprises adding an alkene represented by the following formula (1) to a cyclopentenone represented by the following formula (2) under the action of an alkyllithium and an organic copper reagent to form an adduct, reacting said adduct with a carboxylic acid halide represented by the following formula (3), a carboxylic anhydride represented by the following formula (4) or a mixed carboxylic anhydride represented by the following formula (5) to obtain a reaction product containing a prostaglandin derivative represented by the following formula 6, and then treating said reaction product with a nitrogen-containing compound:
- wherein
- R1 is an alkanoyl group or an alkanoyl group containing a hereto atom in the alkyl group moiety,
- R2 is an alkyl group or an alkyl group containing a hereto atom,
- each of R3 and R4 which are independent of each other, is a protecting group for a hydroxyl group or a hydrogen atom,
- R5 is an alkyl group, a substituted alkyl group, a cycloalkyl group, a substituted cycloalkyl group, an alkenyl group or an alkynyl group,
- R6 is an alkanoyl group or an alkanoyl group containing a hereto atom in an alkyl group moiety, and is different from R1,
- Q is an ethylene group or a vinylene group,
- X1 is an iodine atom or a trialkyltin group,
- X2 is a halogen atom, and
- wherein the nitrogen-containing compound is selected from the group consisting of
- (a) an organic carboxylic acid amide compound,
- (b) an organic thiourea compound,
- (c) an organic phosphorous triamide compound,
- (d) an organic phosphoric triamide compounds, and
- (e) an organic amine compound selected from the group consisting of trimethylamine, triethylamine, triisopropylamine, tributylamine, trioctylamine, cyclohexylamine, pyrrolidine, piperidine, N-methylcyclohexylamine, aniline, N-methylaniline, and N,N-dimethylaniline.
Dependencies are inferred from the claim text.