Process to prepare treprostinil, the active ingredient in remodulin®
US-2015376106-A1 · Dec 31, 2015 · US
US10766853B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10766853-B2 |
| Application number | US-201816495370-A |
| Country | US |
| Kind code | B2 |
| Filing date | Feb 28, 2018 |
| Priority date | Mar 20, 2017 |
| Publication date | Sep 8, 2020 |
| Grant date | Sep 8, 2020 |
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The invention relates to a method for preparing aqueous solutions of N,N-dimethylglucamine, characterized by first preparing an adduct of N-methylglucamine and formaldehyde in water at temperatures of between 15° C. and 40° C., and subsequently reacting said adduct to N,N-dimethylglucamine in the presence of a metal catalyst under hydrogen pressure at 20-68° C., followed by secondary hydrogenation at 70-120 bar and 70-110° C. once hydrogen absorption at 20-68° C. is completed.
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The invention claimed is: 1. A process for preparing N,N-dimethylglucamine comprising the step of reacting an aqueous solution of N-methylglucamine first with an aqueous solution of formaldehyde at 15-40° C. and subsequently, at a pressure of 20-120 bar and a temperature T=30-68° C., with hydrogen under metal catalysis, wherein, after absorption of hydrogen has completed at 20-68° C., a further, after-hydrogenation is added at 70-120 bar and at 70-110° C. 2. The process as claimed in claim 1 , wherein the metal catalyst is Raney nickel. 3. The process as claimed in claim 1 , which is carried out at a hydrogen pressure of 70-110 bar. 4. The process as claimed in claim 1 , wherein the hydrogenation is carried out at 35-65° C. 5. The process as claimed in claim 1 , wherein the molar ratio of N-methylglucamine to formaldehyde is 1:1 to 1:1.5. 6. The process as claimed in claim 1 , wherein the hydrogenation catalyst is reused more than 5 times. 7. The process as claimed in claim 1 , wherein reaction takes place in a stirred reactor or loop reactor. 8. The process as claimed in claim 1 , wherein the remaining N-methylglucamine content is <2wt %. 9. The process as claimed in claim 1 , wherein the residual formaldehyde content is <0.1 wt %. 10. The process as claimed in claim 1 , in which the Hazen color number of the resulting solution of N,N-dimethylglucamine is <500. 11. The process as claimed in claim 1 , in which the molar ratio of N-methylglucamine to formaldehyde is 1:1 to 1:1.2. 12. The process as claimed in claim 1 , in which the molar ratio of N-methylglucamine to formaldehyde is 1:1.01 to 1:1.08. 13. The process as claimed in claim 1 , wherein the residual N-methylglucamine content is <1 wt %. 14. The process as claimed in claim 1 , wherein the residual N-methylglucamine content is <0.25 wt %. 15. The process as claimed in claim 1 , wherein the hydrogenation is carried out at 40-50° C.
by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups · CPC title
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