Method for producing optically active diamine derivative
AssigneeDaiichi Sankyo Company, Limited
InventorKoutarou Kawanami
Life of this patent
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Abstract
The problem to be solved is to provide an important intermediate for production of an FXa inhibitor. The solution thereto is a method for industrially producing a compound (1) or a compound (4), comprising: [Step 1]: adding a quaternary ammonium salt and a metal azide salt to water to prepare an aqueous solution of an azidification reagent complex comprising quaternary ammonium salt-metal azide salt, and subsequently dehydrating the aqueous solution using an aromatic hydrocarbon solvent to form a mixed solution of the azidification reagent complex comprising quaternary ammonium salt-metal azide salt and the aromatic hydrocarbon solvent with a water content of 0.2% or less; and [Step 2]: adding, to the mixed solution prepared in [Step 1], a compound (2) wherein L represents a leaving group.
Claims18
A method for producing a compound (1) represented by the following formula:
- wherein Boc represents a tert-butoxycarbonyl group,
- the method comprising:
- (i) adding a 1-dodecylpyridinium salt and a metal azide salt to water to prepare an aqueous solution of an azidification reagent complex comprising 1-dodecylpyridinium salt-metal azide salt, and
- subsequently performing azeotropic dehydration of the azidification reagent complex by adding the azidification reagent complex to an aromatic hydrocarbon solvent to form a mixed solution comprising the azidification reagent complex and the aromatic hydrocarbon solvent, wherein the water content of the mixed solution is 0.2% or less;
- and
- (ii) adding, to the mixed solution prepared in step (i), a compound (2) represented by the following formula:
- wherein Boc is as defined above;
- and L represents a leaving group, wherein the leaving group represents a (C1 to C2 alkyl)sulfonyloxy group (wherein the C1 to C2 alkyl group may have one or more identical or different halogeno groups as substituents) or a benzenesulfonyloxy group (wherein the benzene ring may have one or more identical or different groups as substituents selected from a halogeno group, a methyl group, and a nitro group).
A method for producing a compound (1) represented by the following formula:
- wherein Boc represents a tert-butoxycarbonyl group, the method comprising:
- (i) adding an amount of 1 dodecylpyridinium salt and an amount of a metal azide salt to water to prepare an aqueous solution of an azidification reagent complex comprising 1 dodecylpyridinium salt-metal azide salt, and
- subsequently performing azeotropic dehydration of the azidification reagent complex by adding the azidification reagent complex to an aromatic hydrocarbon solvent to form a mixed solution comprising the azidification reagent complex and the aromatic hydrocarbon solvent, wherein the water content of the mixed solution is 0.2% or less;
- and
- (ii) adding, to the mixed solution prepared in Step (i), a compound (2) represented by the following formula:
- wherein Boc is as defined above;
- and L represents a leaving group, wherein the leaving group represents a (C1 to C2 alkyl)sulfonyloxy group (wherein the C1 to C2 alkyl group may have one or more identical or different halogeno groups as substituents) or a benzenesulfonyloxy group (wherein the benzene ring may have one or more identical or different groups as substituents selected from a halogeno group, a methyl group, and a nitro group),
- wherein the amount of the 1 dodecylpyridinium salt added in Step (i) is stoichiometrically in the range of 0.45 to 0.55 molar equivalent with respect to compound (2) in Step (ii), and
- wherein the amount of the metal azide salt added in Step (i) is stoichiometrically in the range of 1.8 to 2.2 molar equivalents with respect to compound (2) in Step (ii).
Dependencies are inferred from the claim text.