Process for producing threo-3-(3,4-dihydroxyphenyl)-L-serine
View Patent ↗The present invention provides a process for producing Droxidopa or a pharmaceutically acceptable salt thereof comprising a step of reacting threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine represented by the formula (1) with methylamine, whereby a process for producing threo-3-(3,4-dihydroxyphenyl)-L-serine (common name: Droxidopa), which is useful as an agent for treatment of peripheral orthostatic hypotension or an agent for treatment of Parkinson's disease, with high production efficiency and without requiring troublesome operations.
1. A process for producing threo-3-(3,4-dihydroxyphenyl)-L-serine or a pharmaceutically acceptable salt thereof comprising a step of reacting threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine with methylamine.
2. A process for producing threo-3-(3,4-dihydroxyphenyl)-L-serine or a pharmaceutically acceptable salt thereof comprising a step of reacting threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine with methylamine, and a step of neutralizing a reaction solution with an acid after a completion of the reaction of threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine with methylamine.
3. The process according to claim 1 , wherein the process comprises a step of neutralizing a reaction solution with an acid after a completion of the reaction of threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine with methylamine, and a step of isolating the formed threo-3-(3,4-dihydroxyphenyl)-L-serine.
4. The process according to claim 3 , wherein pH after the neutralization is adjusted to a range between 4 and 7.5.
5. The process according to claim 1 , wherein a solvent for the reaction of threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine with methylamine is alcohol solvent or mixed solvent of alcohol solvent and water.
6. The process according to claim 5 , wherein the alcohol solvent is methanol.
7. The process according to claim 5 , wherein an amount used of the solvent is 0.5 to 3 times in weight based on threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine.
8. The process according to claim 1 , wherein a reaction temperature during the reaction of threo-N-phthaloyl-3-(3,4-dihydroxyphenyl)-L-serine with methylamine is a range between 35° C. and 60° C.