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US 2011/0034726 A1Published application
Process Of Preparation Of Optically Active Alpha Aminoacetals
AssigneeClariant Specialty Fine Chemicals (France)
InventorsMuriel Albalat, Geraldine Primazot, Didier Wilhelm, Jean-Claude Vallejos
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Abstract
The invention relates to a process for preparing optically active α-aminoacetals by resolution of a racemic mixture or of a mixture of enantiomers via the formation of diastereoisomeric salts, and also novel intermediates in the form of diastereoisomeric salts.
Claims19
A process for preparing optically active α-aminoacetals of formula (R)-(I) or (S)-(I)
- wherein:
- R1 and R2, may be identical or different, and are a linear or branched C1-C12 alkyl group, or else R1 and R2 are joined so as to form a 1,3-dioxolan-2-yl group wherein the 1,3-dioxolan-2-yl group unsubstituted or substituted on positions 4 and/or 5 with one or more linear or branched C1-C6 alkyl substituents, or wherein the 1,3-dioxan-2-yl group is unsubstituted or substituted on positions 4 and/or 5 and/or 6 with at least one linear or branched C1-C6 alkyl substituent;
- R3 is a linear or branched C1-C12 alkyl group;
- a C2-C12 alkenyl group;
- a C2-C12 alkynyl group;
- a C3-C10 cycloalkyl group;
- a C3-C10 cycloalkenyl group;
- a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above;
- a heterocycloalkyl group containing 3 to 10 atoms;
- a heterocycloalkylalkyl group wherein the heterocycloalkyl and alkyl groups are as defined above;
- a monocyclic, bicyclic or tricyclic C6-C14 aryl group;
- a heteroaryl group containing 5 to 14 atoms;
- an arylalkyl group or a heteroarylalkyl group, in which the aryl, heteroaryl and alkyl groups are as defined above;
- a C(═O)R4 group wherein R4 is a linear or branched C1-C12 alkyl group, a cycloalkyl group, a cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, as defined above, or an OR5 group wherein R5 is an H, a linear or branched C1-C12 alkyl group, a C3-C10 cycloalkyl group, a C3-C10 cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, as defined above, or R4 is an NHR6 group wherein R6 is a H, a linear or branched C1-C12 alkyl group, a C3-C10 cycloalkyl group, a C3-C10 cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, as defined above;
- all the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocycloalkyl, heterocyclo-alkylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl radicals above being unsubstituted or substituted;
- the asterisk * signifies that the C atom is an asymmetrical carbon,
- wherein the process comprises the resolution of a compound of formula (I) in racemic form or in the form of mixtures of enantiomers
- wherein R1, R2, R3 and the asterisk * are as defined above, with a resolving agent,
- wherein the process comprises the steps of
- a) reacting a compound of formula (I) with an optically active α-amino acid represented by general formulae (II) to (VI)
- wherein:
- R7 is a linear or branched C1-C12 alkyl group;
- a C3-C10 cycloalkyl group;
- a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above;
- a monocyclic, bicyclic or tricyclic C6-C14 aryl group;
- an arylalkyl group wherein the alkyl and aryl groups are as defined above;
- a heteroaryl group containing 5 to 14 atoms;
- or a heteroarylalkyl group wherein the alkyl and heteroaryl groups are as defined above;
- all the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl radicals being unsubstituted or substituted;
- P is a 9 fluorenylmethoxycarbonyl protective group;
- a —COR8 group wherein R8 is a hydrogen, a linear or branched C1-C6 alkyl group, a monocyclic, bicyclic or tricyclic C6-C14 aryl group or an OR9 group wherein R9 is a linear or branched C1-C6 alkyl group or an arylalkyl group wherein the aryl and alkyl groups are as defined above;
- or an —S(C2)R10 group wherein R10 is a linear or branched C1-C6 alkyl group, a monocyclic, bicyclic or tricyclic C6-C14 aryl group or an arylalkyl group wherein the aryl and alkyl groups are as defined above;
- all the 9-fluorenylmethoxycarbonyl, alkyl, aryl and arylalkyl groups being unsubstituted or substituted;
- X is a carbon or sulphur atom;
- R, R′, R″ and R′″, independently of one another, are at least one hydrogen atom, halogen atom or hydroxyl group or an oxo (═O) group;
- the asterisk * signifies that the C atom is an asymmetrical carbon,
- in a solvent, so as to form diastereoisomeric salts represented by formulae
- wherein R1, R2, R3, R7, P, X, R, R′, R″, R′″ and the asterisk * are as defined above,
- b) separating the diastereoisomeric salts of formulae (VII) to (XI) formed in the medium, and
- c) releasing the optically active α-aminoacetal of formula (R)-(I) or (S)-(I).
37 more elements
A diastereoisomeric salt according to general formulae (VII) to (XI)
- wherein:
- R1 and R2, which may be identical or different, are a linear or branched C1-C12 alkyl group, or else R1 and R2 are joined so as to form a 1,3-dioxolan-2-yl group wherein the 1,3-dioxolan-2-yl group is unsubstituted or substituted on positions 4 and/or 5 with one or more linear or branched C1-C6 alkyl substituents, or is a 1,3-dioxan-2-yl group which is unsubstituted or substituted on positions 4 and/or 5 and/or 6 with one or more linear or branched C1-C6 alkyl substituents;
- R3 is a linear or branched C1-C12 alkyl group;
- a C2-C12 alkenyl group;
- a C2-C12 alkynyl group;
- a C3-C10 cycloalkyl group;
- a C3-C10 cycloalkenyl group;
- a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above;
- a heterocycloalkyl group containing 3 to 10 atoms;
- a heterocyclo-alkylalkyl group wherein the heterocycloalkyl and alkyl groups are as defined above;
- a monocyclic, bicyclic or tricyclic C6-C14 aryl group;
- a heteroaryl group containing 5 to 14 atoms;
- an arylalkyl group or a heteroarylalkyl group, wherein the aryl, heteroaryl and alkyl groups are as defined above;
- a C(═O)R4 group wherein R4 is a linear or branched C1-C12 alkyl group, a cycloalkyl group, a cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, as defined above, or an OR5 group wherein R5 is a H, a linear or branched C1-C12 alkyl group, a C3-C10 cycloalkyl group, a C3-C10 cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, as defined above, or R4 is a NHR6 group wherein R6 is a H, a linear or branched C1-C12 alkyl group, a C3-C10 cycloalkyl group, a C3-C10 cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, as defined above;
- all the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl radicals above being unsubstituted or substituted;
- the asterisk * signifies that the C atom is an asymmetrical carbon,
- R7 is a linear or branched C1-C12 alkyl group;
- a C3-C10 cycloalkyl group;
- a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above;
- a monocyclic, bicyclic or tricyclic C6-C14 aryl group;
- an arylalkyl group wherein the alkyl and aryl groups are as defined above;
- a heteroaryl group containing 5 to 14 atoms;
- or a heteroarylalkyl group wherein the alkyl and heteroaryl groups are as defined above;
- all the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl radicals being unsubstituted or substituted;
- P is a 9-fluorenylmethoxycarbonyl protective group;
- a —COR8 group wherein R8 is a hydrogen, a linear or branched C1-C6 alkyl group, a monocyclic, bicyclic or tricyclic C6-C14 aryl group or an OR9 group wherein R9 is a linear or branched C1-C6 alkyl group or an arylalkyl group wherein the aryl and alkyl groups are as defined above;
- or an —S(C2)R10 group wherein R10 is a linear or branched C1-C6 alkyl group, a monocyclic, bicyclic or tricyclic C6-C14 aryl group or an arylalkyl group wherein the aryl and alkyl groups are as defined above;
- all the 9-fluorenylmethoxycarbonyl, alkyl, aryl and arylalkyl groups being unsubstituted or substituted;
- X is a carbon or sulphur atom;
- R, R′, R″ and R′″, independently of one another, are at least one hydrogen atom, halogen atom, hydroxyl group or an oxo (═O) group.
27 more elements
Dependencies are inferred from the claim text.