Process for deacetalisation of α aminoacetals

1. A process for the preparation of a N-protected α-aminoaldehyde, in the racemic or optically active form, comprising the steps of:

protecting the amine functional group of the corresponding α-aminoacetal with an arylalkyloxycarbonyl group of general formula (I):

wherein:

R is a hydrogen, a phenyl group or a linear or branched C 1 -C 6 alkyl group,

Ar is a phenyl group, a naphthyl group or an anthryl group, optionally substituted by one or more halogen, phenyl, linear or branched C 1 -C 6 alkyl, linear or branched C 1 -C 6 alkoxy, nitro, cyano or methylsulphinyl groups, and

deacetalizing the acetal functional group of the said N-protected α-aminoacetal using formic acid.

2. A process according to claim 1 , wherein the arylalkyloxycarbonyl group is chosen from benzyloxycarbonyl, 4-phenylbenzyloxycarbonyl, 2-methyl-benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxy-carbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyl-oxycarbonyl, 4-methylsulphinylbenzyloxycarbonyl, 9-anthrylmethyloxycarbonyl and diphenylmethyloxycarbonyl.

3. A process according to claim 1 , wherein the N-protected α-aminoacetal is in the racemic form, of formula (II):

wherein:

R 1 and R 2 , are identical or different and are a linear or branched C 1 -C 12 alkyl group,

or else R 1 and R 2 are joined to form a 1,3-dioxolan-2-yl group unsubstituted or substituted on the 4 and/or 5 position(s) by one or more linear or branched C 1 -C 6 alkyl substituents or a 1,3-dioxan-2-yl group unsubstituted or substituted on the 4 and/or 5 and/or 6 position(s) by one or more linear or branched C 1 -C 6 alkyl substituents;

R 3 is a hydrogen; a linear or branched C 1 -C 12 alkyl group; a C 2 -C 12 alkenyl group; a C 2 -C 12 alkynyl group; a C 3 -C 10 cycloalkyl group; a C 3 -C 10 cycloalkenyl group; a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above; a heterocycloalkyl group including 3 to 10 atoms; a heterocycloalkylalkyl group wherein the heterocycloalkyl and alkyl groups are as defined above; a monocyclic, bicyclic or tricyclic C 6 -C 14 aryl group; a heteroaryl group including 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)R 4 group wherein R 4 is a linear or branched C 1 -C 12 alkyl group, a C 3 -C 10 cycloalkyl group, a C 3 -C 10 cycloalkenyl group, a heterocycloalkyl group including 3 to 10 atoms, an aryl group or a heteroaryl group as defined above, or R 4 is an OR 5 group wherein R 5 is a hydrogen, a linear or branched C 1 -C 12 alkyl group, a C 3 -C 10 cycloalkyl group, a C 3 -C 10 cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group as defined above, or R 4 is an NHR 6 group wherein-R 6 is a hydrogen, a linear or branched C 1 -C 12 alkyl group, a C 3 -C 10 cycloalkyl group, a C 3 -C 10 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 or heteroarylalkyl radicals above being unsubstituted or substituted; and

P is a group of formula (I),

comprising the step of deacetalizing the acetal functional group using formic acid in order to obtain the N-protected α-aminoaldehyde, in the racemic form, of formula (III):

wherein R 3 and P are defined above.

4. A process according to claim 1 , wherein the N-protected α-aminoacetal, is in the optically active form, of formula (R)-(II) or (S)-(II):

wherein:

the asterisk * means that the carbon atom is an asymmetric carbon,

R 1 and R 2 , are identical or different, and are a linear or branched C 1 -C 12 alkyl group,

or else R 1 and R 2 are joined to form a 1,3-dioxolan-2-yl group unsubstituted or substituted on the 4 and/or 5 position(s) by one or more linear or branched C 1 -C 6 alkyl substituents or a 1,3-dioxan-2-yl group unsubstituted or substituted on the 4 and/or 5 and/or 6 position(s) by one or more linear or branched C 1 -C 6 alkyl substituents;

R 3 is a linear or branched C 1 -C 12 alkyl group; a C 2 -C 12 alkenyl group; a C 2 -C 12 alkynyl group; a C 3 -C 10 cycloalkyl group; a C 3 -C 10 cycloalkenyl group; a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are defined above; a heterocycloalkyl group including 3 to 10 atoms; a heterocycloalkylalkyl group wherein the heterocycloalkyl and alkyl groups are-defined above; a monocyclic, bicyclic or tricyclic C 6 -C 14 aryl group; a heteroaryl group including 5 to 14 atoms; an arylalkyl group or a heteroarylalkyl group wherein the aryl, heteroaryl and alkyl groups are defined above; a C(═O)R 4 group in which R 4 is a linear or branched C 1 -C 12 alkyl group, a C 3 -C 10 cycloalkyl group, a C 3 -C 10 cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group as defined above, or R 4 is an OR 5 group wherein R 5 is a hydrogen, a linear or branched C 1 -C 12 alkyl group, a C 3 -C 10 cycloalkyl group, a C 3 -C 10 cycloalkenyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group as defined above, or R 4 is an NHR 6 group wherein R 6 is a hydrogen, a linear or branched C 1 -C 12 alkyl group, a C 3 -C 10 cycloalkyl group, a C 3 -C 10 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 or heteroarylalkyl radicals above being unsubstituted or substituted; and

P is a group of formula (I),

comprising the step of deacetalizing the acetal functional group using formic acid in order to obtain the N-protected α-aminoaldehyde, in optically active form, of formula (R)-(III) or (S)-(III):

wherein:

the asterisk * means that the carbon atom is an asymmetric carbon, and R 3 and P are defined above.

5. A process according to claim 1 , wherein the N-protected α-aminoacetal, is in the optically active form, of formula (R)-(IV) or (S)-(IV):

wherein:

the asterisk * means that the carbon atom is an asymmetric carbon,

R 1 and R 2 , are identical or different, and are a linear or branched C 1 -C 12 alkyl group or else

R 1 and R 2 are joined to form a 1,3-dioxolan-2-yl group unsubstituted or substituted on the 4 and/or 5 position(s) by one or more linear or branched C 1 -C 6 alkyl substituents or a 1,3-dioxan-2-yl group unsubstituted or substituted on the 4 and/or 5 and/or 6 position(s) by one or more linear or branched C 1 -C 6 alkyl substituents;

R 7 is a linear or branched C 1 -C 12 alkyl group; a C 2 -C 12 alkenyl group, a C 2 -C 12 alkynyl group; a C 3 -C 10 cycloalkyl group; a C 3 -C 10 cycloalkenyl group; a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are defined above; a heterocycloalkyl group including 3 to 10 atoms; a heterocycloalkylalkyl group wherein the heterocycloalkyl and alkyl groups are defined above; an arylalkyl group in which the monocyclic, bicyclic or tricyclic aryl group is a C 6 -C 14 aryl group and the alkyl group is as defined above; a heteroarylalkyl group wherein the heteroaryl group includes 5 to 14 atoms and the alkyl group is defined above; all the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, arylalkyl or heteroarylalkyl radicals above being unsubstituted or substituted; and

P is a group of formula (I),

comprising the step of deacetalizing the acetal functional group using formic acid in order to obtain the N-protected α-aminoaldehyde, in the optically active form, of formula (R)-(V) or (S)-(V):

wherein:

the asterisk * means that the carbon atom is an asymmetric carbon;

R 7 and P are defined above.

6. A process according to claim 1 , wherein in the deacetalizing step, the formic acid is used in a proportion of 1 to 30 molar equivalents.

7. A process according to claim 1 , wherein the deacetalizing step is carried out in the presence of water in an amount of between 0.01 and 0.1 equivalent by weight with respect to the formic acid.

8. A compound of formula (II), (R)-(II) or (S)-(II):

wherein:

R 1 and R 2 , are identical or different, and are a linear or branched C 1 -C 12 alkyl group;

R 3 is a cycloalkylalkyl group wherein the cycloalkyl group is a C 3 -C 10 cycloalkyl group and the linear or branched alkyl group is a C 1 -C 12 alkyl group;

P is a benzyloxycarbonyl group, and

the asterisk * means that the carbon atom is an asymmetric carbon.

9. A process according to claim 1 , wherein in the deacetalizing step, the formic acid is used in a proportion of 20 to 25 molar equivalents.

10. A process according to claim 1 , wherein in the deacetalizing step is carried out in the presence of water in an amount of 0.05 equivalent by weight, with respect to the formic acid.