Method for synthesis of acrylamide derivatives
View Patent ↗The present invention relates to a method for synthesis of an acrylamide derivative, starting with dissolving a salt of a nucleophilic amine in water to form an aqueous solution and desalting said solution with a base, comprising the following steps: a) addition of dissolved activated acrylic acid derivative to said solution; b) acidification of aqueous phase; and c) extraction of said aqueous phase.
1. A method for synthesis of an acrylamide derivative, starting with dissolving a salt of a nucleophilic amine in water to form an aqueous solution and desalting said solution with a base, comprising the following steps:
a) addition of dissolved activated acrylic acid derivative to said solution;
b) acidification of aqueous phase; and
c) extraction of said aqueous phase.
2. The method of claim 1 , wherein the acrylamide derivative is an immobiline.
3. The method of claim 2 , wherein the acrylamide derivative is acrylamido agmatine.
4. The method of claim 3 , wherein the salt is an agmatine salt.
5. The method of claim 1 , wherein the extraction in step c) is performed with an organic solvent.
6. The method of claim 5 , wherein the organic solvent is MIBK (methyl isobutyl ketone).
7. The method of claim 1 , wherein the acrylic acid derivative is an activated acrylic acid derivative selected from the group consisting of acryloyl chloride, acrylic acid N-hydroxysuccinimide ester, pentafluorophenyl acrylate, pentachlorophenylacrylate, and 4-nitrophenyl acrylate.
8. The method of claim 1 , wherein the desalting is with NaOH, TEA (triethylamine), DIPEA (diisopropylethylamine), or K 2 CO 3 .
9. The method of claim 1 , further comprising fixing pH to 7.
10. The method of claim 1 , comprising, before step b),
i) basification of aqueous phase to a pH above the pKa of the organic base, and
ii) extraction of aqueous phase with an organic solvent to remove the organic base.
11. The method of claim 1 , wherein agmatine sulphate is dissolved, desalted with K 2 CO 3 and comprising the following steps:
a) addition of acryloyl chloride;
b) acidification to pH 1-4;
c) filtration;
d) extraction with MIBK; and
e) pH adjustment to pH 7.
12. The method of claim 11 , wherein the acidification pH is 2.3.