Process for the preparation of substituted cycloserines
View Patent ↗The present invention relates to processes for the preparation of substituted cycloserine compounds of formula (I) wherein R 1 is C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 3 -C 6 cycloalkyl, aryl or aryl substituted by one to five R 11 , or aryl-C 1 -C 4 alkylene or aryl-C 1 -C 4 alkylene substituted by one to five R 11 ; and each R 11 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano or halogen; The invention also relates to intermediates produced by the processes. Compounds of formula (I) are useful intermediates for the production of compounds in the agricultural and pharmaceutical fields.
1. A process for the preparation of a compound of formula (I)
wherein
R 1 is C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, aryl or aryl substituted by one to five R 11 , or aryl-C 1 -C 4 alkylene or aryl-C 1 -C 4 alkylene substituted by one to five R 11 ; and
each R 11 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano or halogen;
comprising
a-1. reacting the compound of formula (II)
with the compound of formula (III)
in the presence of a suitable acid
wherein
R 2 is a leaving group selected from halogen, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8 haloalkylsulfonyloxy, C 1 -C 8 arylsulfonyloxy or C 1 -C 8 arylsulfonyloxy substituted by one to five R 11 , or a phosphonate ester; and each R 11 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano or halogen;
to produce the compound of formula (IV) or a salt thereof
wherein R 1 and R 2 are as defined for the compound of formula (I) and formula (III)
and
a-2. converting the compound of formula (IV) to the compound of formula (I) in the presence of a suitable base.
2. A process for the preparation of a compound of formula (IV)
comprising
a-1. reacting the compound of formula (II)
with the compound of formula (III)
in the presence of a suitable acid
wherein
R 1 is C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, aryl or aryl substituted by one to five R 11 , or aryl-C 1 -C 4 alkylene or aryl-C 1 -C 4 alkylene substituted by one to five R 11 ;
R 2 is a leaving group selected from halogen, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8 haloalkylsulfonyloxy, C 1 -C 8 arylsulfonyloxy or C 1 -C 8 arylsulfonyloxy substituted by one to five R 11 , or a phosphonate ester;
each R 11 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano or halogen.
3. A process for the preparation of a compound of formula (I)
comprising the step a-2
a-2. converting the compound of formula (IV)
to the compound of formula (I) in the presence of a suitable base
wherein
R 1 is C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, aryl or aryl substituted by one to five R 11 , or aryl-C 1 -C 4 alkylene or aryl-C 1 -C 4 alkylene substituted by one to five R 11 ;
R 2 is C 1 -C 8 alkylsulfonyloxy, C 1 -C 8 haloalkylsulfonyloxy, C 1 -C 8 arylsulfonyloxy or C 1 -C 8 arylsulfonyloxy substituted by one to five R 11 , or a phosphonate ester; and
each R 11 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano or halogen.
4. A compound of formula (IV)
wherein
R 1 is C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, aryl or aryl substituted by one to five R 11 , or aryl-C 1 -C 4 alkylene or aryl-C 1 -C 4 alkylene substituted by one to five R 11 ;
R 2 is C 1 -C 8 alkylsulfonyloxy, C 1 -C 8 haloalkylsulfonyloxy, C 1 -C 8 arylsulfonyloxy or C 1 -C 8 arylsulfonyloxy substituted by one to five R 11 , or a phosphonate ester; and
each R 11 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano or halogen;
or a salt or N-oxide thereof.