The present invention discloses a process for recovery of a boronic acid of formula R.sub.3B(OH).sub.2, wherein R.sub.3 is selected from the group consisting of C.sub.1-C.sub.6 linear or branched alkyl, C.sub.3-C.sub.6 cycloalkyl, and C.sub.6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, and phenyl, comprising admixing the boronic acid with a water-immiscible organic solvent in a weight ratio between the boronic acid and the water-immiscible organic solvent from 1:10 to 1:20, adding an aqueous solution to a final pH of neutral, and partitioning the boronic acid into an organic water-immiscible phase and recovery of the organic water-immiscible phase.

The present invention discloses a process for recovery of a boronic acid of formula R.sub.3B(OH).sub.2, wherein R.sub.3 is selected from the group consisting of C.sub.1-C.sub.6 linear or branched alkyl, C.sub.3-C.sub.6 cycloalkyl, and C.sub.6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, and phenyl, comprising admixing the boronic acid with a water-immiscible organic solvent in a weight ratio between the boronic acid and the water-immiscible organic solvent from 1:10 to 1:20, adding an aqueous solution to a final pH of neutral, and partitioning the boronic acid into an organic water-immiscible phase and recovery of the organic water-immiscible phase.

The present invention discloses a process for recovery of a boronic acid of formula R.sub.3B(OH).sub.2, wherein R.sub.3 is selected from the group consisting of C.sub.1-C.sub.6 linear or branched alkyl, C.sub.3-C.sub.6 cycloalkyl, and C.sub.6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, and phenyl, comprising admixing the boronic acid with a water-immiscible organic solvent in a weight ratio between the boronic acid and the water-immiscible organic solvent from 1:10 to 1:20, adding an aqueous solution to a final pH of neutral, and partitioning the boronic acid into an organic water-immiscible phase and recovery of the organic water-immiscible phase.

The present invention generally relates to a process of preparing iosimenol and a process of preparing a crystal of iosimenol, as well as a crystal of iosimenol prepared by these processes.

The present invention generally relates to a process of preparing iosimenol and a process of preparing a crystal of iosimenol, as well as a crystal of iosimenol prepared by these processes.

The present invention is related to the synthesis of 4-hydroxymethyl-2-oxazolidinone (serinol carbamate, SC), which can be subsequently hydrolyzed to 2-amino-1,3-propanediol (serinol), by reacting glycerol and urea: (I) In general, glycerol is heated with urea and a catalyst, with or without a solvent, to give mainly 4-hydroxymethyl-2-oxazolidinone (serinol carbamate, SC), which is hydrolyzed in the next step to 2-amino-1,3-propanediol (serinol). Alternatively, glycerol 1,2-carbonate can be used instead of glycerol. Serinol obtained by the process of the invention may be used in the synthesis of Iopamidol.

##STR00001##

The present invention is related to the synthesis of 4-hydroxymethyl-2-oxazolidinone (serinol carbamate, SC), which can be subsequently hydrolyzed to 2-amino-1,3-propanediol (serinol), by reacting glycerol and urea: (I) In general, glycerol is heated with urea and a catalyst, with or without a solvent, to give mainly 4-hydroxymethyl-2-oxazolidinone (serinol carbamate, SC), which is hydrolyzed in the next step to 2-amino-1,3-propanediol (serinol). Alternatively, glycerol 1,2-carbonate can be used instead of glycerol. Serinol obtained by the process of the invention may be used in the synthesis of Iopamidol.

##STR00001##

The present invention discloses a process for the preparation of Iopamidol of formula (II)

##STR00001##

and comprising the following steps: a) reacting the Compound (I) wherein X is OR.sub.2 or R.sub.3, and wherein R.sub.2 and R.sub.3 are a C.sub.1-C.sub.6 linear or branched alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl and phenyl, with the acylating agent (S)-2-(acetyloxy)propanoyl chloride in a reaction medium to provide the acetyloxy derivative of Compound (I); b) hydrolyzing the intermediate from step a) with an aqueous solution at a pH comprised from 0 to 7, by adding water or a diluted alkaline solution such as sodium hydroxide or potassium hydroxide, freeing the hydroxyls from the boron-containing protective groups, obtaining the N-(S)-2-(acetyloxy)propanoyl derivative of Compound (II); c) alkaline hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain Iopamidol (II) and optional recovery of the boron derivative from the solution obtained in step b).

The boron-containing protective group is versatile, efficient and recyclable. A one-pot synthesis, without intermediate isolation is provided, leading to a decreasing of recovered and recycled solvents and a significant increasing in the yield, representing a significant advantage in terms of cost-effectiveness of the entire process and environmental awareness.

The present invention discloses a process for the preparation of Iopamidol of formula (II)

##STR00001##

and comprising the following steps: a) reacting the Compound (I) wherein X is OR.sub.2 or R.sub.3, and wherein R.sub.2 and R.sub.3 are a C.sub.1-C.sub.6 linear or branched alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl and phenyl, with the acylating agent (S)-2-(acetyloxy)propanoyl chloride in a reaction medium to provide the acetyloxy derivative of Compound (I); b) hydrolyzing the intermediate from step a) with an aqueous solution at a pH comprised from 0 to 7, by adding water or a diluted alkaline solution such as sodium hydroxide or potassium hydroxide, freeing the hydroxyls from the boron-containing protective groups, obtaining the N-(S)-2-(acetyloxy)propanoyl derivative of Compound (II); c) alkaline hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain Iopamidol (II) and optional recovery of the boron derivative from the solution obtained in step b).

The boron-containing protective group is versatile, efficient and recyclable. A one-pot synthesis, without intermediate isolation is provided, leading to a decreasing of recovered and recycled solvents and a significant increasing in the yield, representing a significant advantage in terms of cost-effectiveness of the entire process and environmental awareness.

The present invention discloses a process for the preparation of Iopamidol of formula (II)

##STR00001##

and comprising the following steps: a) reacting the Compound (I) wherein X is OR.sub.2 or R.sub.3, and wherein R.sub.2 and R.sub.3 are a C.sub.1-C.sub.6 linear or branched alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl and phenyl, with the acylating agent (S)-2-(acetyloxy)propanoyl chloride in a reaction medium to provide the acetyloxy derivative of Compound (I); b) hydrolyzing the intermediate from step a) with an aqueous solution at a pH comprised from 0 to 7, by adding water or a diluted alkaline solution such as sodium hydroxide or potassium hydroxide, freeing the hydroxyls from the boron-containing protective groups, obtaining the N-(S)-2-(acetyloxy)propanoyl derivative of Compound (II); c) alkaline hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain Iopamidol (II) and optional recovery of the boron derivative from the solution obtained in step b).

The boron-containing protective group is versatile, efficient and recyclable. A one-pot synthesis, without intermediate isolation is provided, leading to a decreasing of recovered and recycled solvents and a significant increasing in the yield, representing a significant advantage in terms of cost-effectiveness of the entire process and environmental awareness.