Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):

##STR00001##

and/or a salt thereof, wherein R.sub.1 is OH or OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

The present invention relates to processes for the preparation of N-protected 4-((2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxamido)piperidine-1-carboxylates. Such compounds have application in the preparation of beta-lactamase inhibitors such as 7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamides and esters, in particular, the beta lactamase inhibitor, (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. The present invention also encompasses intermediates useful in the disclosed processes and methods for their preparation.

The present invention relates to processes for the preparation of N-protected 4-((2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxamido)piperidine-1-carboxylates. Such compounds have application in the preparation of beta-lactamase inhibitors such as 7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamides and esters, in particular, the beta lactamase inhibitor, (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. The present invention also encompasses intermediates useful in the disclosed processes and methods for their preparation.

The present invention relates to processes for the preparation of N-protected 4-((2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxamido)piperidine-1-carboxylates. Such compounds have application in the preparation of beta-lactamase inhibitors such as 7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamides and esters, in particular, the beta lactamase inhibitor, (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. The present invention also encompasses intermediates useful in the disclosed processes and methods for their preparation.

The invention relates to a solvent-free green ammoximation process based on membrane distribution with a procedure as: adding TS-1 catalyst and ketone into a reactor in advance; setting the stirring speed and reaction temperature; after reaching the set temperature, adding a certain amount of ammonia and hydrogen peroxide into a reaction solution, wherein the hydrogen peroxide is fed in a way of using membrane as a distributor, the ammonia is fed in a continuous or semi-continuous manner; oxime is produced upon the reaction. The advantages of the invention include the mild reaction conditions, high reacting efficiency, simple operation and environmentally-friendly process. And there is no need to add any solvent during the reaction process. During the ammoximation reaction, both the conversion rate of the ketone and the selectivity of the oxime can be over 98.0%.

The invention relates to a solvent-free green ammoximation process based on membrane distribution with a procedure as: adding TS-1 catalyst and ketone into a reactor in advance; setting the stirring speed and reaction temperature; after reaching the set temperature, adding a certain amount of ammonia and hydrogen peroxide into a reaction solution, wherein the hydrogen peroxide is fed in a way of using membrane as a distributor, the ammonia is fed in a continuous or semi-continuous manner; oxime is produced upon the reaction. The advantages of the invention include the mild reaction conditions, high reacting efficiency, simple operation and environmentally-friendly process. And there is no need to add any solvent during the reaction process. During the ammoximation reaction, both the conversion rate of the ketone and the selectivity of the oxime can be over 98.0%.

The invention relates to a solvent-free green ammoximation process based on membrane distribution with a procedure as: adding TS-1 catalyst and ketone into a reactor in advance; setting the stirring speed and reaction temperature; after reaching the set temperature, adding a certain amount of ammonia and hydrogen peroxide into a reaction solution, wherein the hydrogen peroxide is fed in a way of using membrane as a distributor, the ammonia is fed in a continuous or semi-continuous manner; oxime is produced upon the reaction. The advantages of the invention include the mild reaction conditions, high reacting efficiency, simple operation and environmentally-friendly process. And there is no need to add any solvent during the reaction process. During the ammoximation reaction, both the conversion rate of the ketone and the selectivity of the oxime can be over 98.0%.

There is disclosed a process for the co-production of long chain -amino acid and long chain dibasic acid, comprising: (1) reacting long chain ketoacid derivative with hydroxylamine or subjecting ketoacid derivative to an ammoximation to yield oxime derivative; (2) subjecting oxime derivative to Beckmann rearrangement to yield a mixture of mixed amide derivatives; (3) hydrolyzing the mixed amide derivatives to produce long chain -amino acid and long chain dibasic acid.

There is disclosed a process for the co-production of long chain -amino acid and long chain dibasic acid, comprising: (1) reacting long chain ketoacid derivative with hydroxylamine or subjecting ketoacid derivative to an ammoximation to yield oxime derivative; (2) subjecting oxime derivative to Beckmann rearrangement to yield a mixture of mixed amide derivatives; (3) hydrolyzing the mixed amide derivatives to produce long chain -amino acid and long chain dibasic acid.

There is disclosed a process for the production of long chain amino acid and long chain dibasic acid, comprising: (1) reacting long chain keto fatty acid with hydroxylamine or subjecting keto fatty acid to an ammoximation reaction to yield an oxime fatty acid; (2) reacting the oxime fatty acid with an alcohol or a primary amine or a secondary amine to prepare an ester or amide; (3) subjecting the oxime fatty acid ester or amide to the Beckmann rearrangement to yield a mixture of two amide fatty acids; (4) hydrolyzing the mixed amide fatty acids to produce long chain amino acid, long chain dibasic acid, short chain alkylamine, and alkanoic acid.