Process for producing α-aminoketone derivatives
AssigneeAjinomoto Co., Inc.
InventorsTomoyuki Onishi, Takashi Nakano, Naoko Hirose, Takayoshi Torii, Masakazu Nakazawa, Kunisuke Izawa
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Abstract
A process for producing α-amino-dihalogenated methyl ketone derivatives by reacting an N-protected α-amino acid ester with a dihalomethyl lithium is provided. This process is suitable for the production on an industrial scale and by this process, α-amino-dihalogenated methyl ketone derivatives and β-amino-α-hydroxycarboxylic acid derivatives can be obtained efficiently and economically advantageously.
Claims19
A process for Producing an α-amino-dihalogenated methyl ketone of formula (3):
- wherein either B3 or B4 is a carbamate-type protecting group and the other is a hydrogen atom;
- A represents a hydrogen atom, an unsubstituted alkyl group having 1 to 10 carbon atoms, a substituted alkyl group having 1 to 10 carbon atoms, an unsubstituted aryl group having 6 to 15 carbon atoms, a substituted aryl group having 6 to 15 carbon atoms an unsubstituted aralkyl group having 7 to 20 carbon atoms, a substituted aralkyl group having 7 to 20 carbon atoms, or a group corresponding thereto which contains a hetero atom in the carbon skeleton;
- and X1 and X2 independently represent a chlorine atom or a bromine atom,
- which comprises reacting an N-protected α-amino acid ester of formula (1):
- wherein either B1 or B2 is a carbamate-type protecting group and the other is a hydrogen atom, R1 represents an unsubstituted lower alkyl group, substituted lower alkyl group, an unsubstituted aralkyl group, a substituted aralkyl group, a substituted aryl group or an unsubstituted aryl group, and A is as defined above
- with a dihalomethyl lithium of formula (2)
- wherein X1 and X2 are as defined above.
A process for producing a β-amino-α-hydroxycarboxylic acid of formula (4):
- wherein B5 and B6 independently represent a hydrogen atom or an amino protecting group, or B5 and B6 together form an imine-type protecting group, and A represents a hydrogen atom, an unsubstituted alkyl group having 1 to 10 carbon atoms, a substituted alkyl group having 1 to 10 carbon atoms, an unsubstituted aryl group having 6 to 15 carbon atoms, a substituted aryl group having 6 to 15 carbon atoms, an unsubstituted aralkyl group having 7 to 20 carbon atoms, a substituted aralkyl group having 7 to 20 carbon atoms, or a group corresponding thereto which contains a hetero atom in the carbon skeleton,
- which comprises reacting an N-protected α-amino acid ester of formula (1):
- wherein B1 and B2 independently represent a hydrogen atom or an amino protecting group, or B1 and B2 together form an imine-type protecting group, wherein B1 and B2 are not a hydrogen atom at the same time, R1 represent an unsubstituted lower alkyl group, a substituted lower alkyl group, an unsubstituted aralkyl group, a substituted aralkyl group, a substituted aryl group, or an unsubstituted aryl group, and A is as defined above
- with a dihalomethyl lithium of formula (2):
- wherein X1 and X2 independently represent a chlorine atom or a bromine atom to form an α-amino-dihalogenated methyl ketone of formula (3):
- wherein B3 and B4 independently represent a hydrogen atom or an amino protecting group, or B3 and B4 together form an imine-type protecting group, and A, X1 and X2 are as defined above;
- and
- hydrolyzing in the presence of a base the α-amino-dihalogenated methyl ketone of formula (3).
Dependencies are inferred from the claim text.