Process for preparing 2-amino malonic acid derivatives and 2-amino-1,3-propanediol derivatives, and intermediates for preparing the same

A process for preparing a compound of the formula (6):

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group, comprising:
• reacting a compound of the formula (7) and 2-(N-substituted)amino malonic acid diester of the formula (3):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• Z is a leaving group,
• wherein
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group.

A process for preparing 2-amino malonic acid derivatives of the formula (1):

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group, comprising:
• reacting a compound of the formula (7) and 2-(N-substituted)amino malonic acid diester of the formula (3) to obtain a compound of the formula (6):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• Z is a leaving group,
• wherein
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group,
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group, and
• reducing the compound of the formula (6).

A process for preparing a compound of the formula (6):

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group, comprising:
• converting a hydroxyl group of a compound of the formula (5) to a leaving group to obtain a compound of a formula (7):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms, and
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• Z is a leaving group, and
• reacting the compound of the formula (7) and 2-(N-substituted)amino malonic acid diester of the formula (3):
• wherein
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group.

A process for preparing a compound of the formula (6):

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group, comprising:
• deacylating a compound of the formula (9) to obtain a compound of the formula (5):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• R5 is an acyl type protecting group,
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms, and
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• converting the hydroxyl group of the compound of the formula (5) to a leaving group to obtain the compound of the formula (7):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• Z is a leaving group, and
• reacting the compound of the formula (7) and 2-(N-substituted)amino malonic acid diester of the formula (3):
• wherein
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group.

A process for preparing a compound of the formula (6):

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group, comprising:
• reacting a compound of the formula (11) and a compound of the formula (15) to obtain a compound of the formula (7):
• wherein
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• X is a halogen,
• wherein
• A is a linear or branched alkylene having from 1 to 10 carbon atoms, and
• Z is a leaving group,
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• Z is a leaving group, and
• reacting the compound of the formula (7) and 2-(N-substituted)amino malonic acid diester of the formula (3):
• wherein
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group.

A process for preparing 2-amino-1,3-propanediol derivatives of the formula (17):

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• R4, R6and R7are the same or different, and are hydrogen or protecting groups, comprising:
• reducing a compound of the formula (19):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• R4, R6, R7 and R8 are the same or different, and are hydrogen or protecting groups.

A process for preparing 2-amino-1,3-propanediol derivatives of the formula (17):

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• R4, R6 and R7 are the same or different, and are hydrogen or protecting groups, comprising:
• reducing a compound of the formula (6) and adding a protecting group, or deprotecting to obtain a compound of the formula (19):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group,
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• R4, R6, R7 and R8 are the same or different, and are hydrogen or protecting groups, and
• reducing the compound of the formula (19).

A process for preparing 2-amino-1,3-propanediol-derivatives of the formula (17),

• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• R4, R6 and R7 are the same or different, and are hydrogen or a protecting group, comprising:
• reacting the compound of the formula (7) and 2-(N-substituted)amino malonic acid diester of the formula (3) to obtain a compound of the formula (6),
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• Z is a leaving group,
• wherein
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group,
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms,
• R2 and R3 are the same or different, and are lower alkyl or aralkyl, and
• R4 is a protecting group,
• reducing the compound of the formula (6) and adding a protecting group, or deprotecting to obtain a compound of the formula (19):
• wherein
• A is a linear or branched chain alkylene having from 1 to 10 carbon atoms,
• R1 is a linear or branched chain alkyl having from 2 to 20 carbon atoms, and
• R4, R6, R7 and R8 are the same or different, and are hydrogen or protecting groups, and
• reducing the compound of the formula (19).