CLEANING METHOD OF 3-GIDROKSIAMIDINOFENILALANINA by precipitation and recrystallization of salts of aromatic sulfonic acids

摘要

1. derivatives of 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 cleaning method, comprising the following steps:;(a) in the appendix (u0441u0443u043bu044cu0444u043eu043du043eu0432u043eu0439 acid to the solution, not u043eu0431u00a0u0437u0430u0442u0435u043bu044cu043du043e u0437u0430u0433u0440u00a0u0437u043du0435u043du043du043eu0433u043e derivative 3 u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 u0434u043bu00a0 u043fu043eu043bu0443u0447u0435u043du0438u00a0 residue.;(b) the obtained in stage (a) in the water, and;(c) u0440u0435u043au0443u043fu0435u0440u0430u0446u0438u00a0 free derivative 3 u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 from sludges.;2. method for u0441u0443u043bu044cu0444u043eu043du043eu0432u043eu0439 acid (1 in which the phase (a) u00a0u0432u043bu00a0u0435u0442u0441u00a0 acid armstrong.;3. method for 1, in which the derivative of 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 has the formula (i):;,;in which r1 refers to a group of the formula where r4 is;(i), in particular the c1 - c6 - u0430u043bu043au0438u043b -, c1 - c3 u0430u043bu043au043eu043au0441u0438 -, hydroxyl -, u043au0430u0440u0431u043eu043au0441u0438u043b - sulfonyl -, nitro -, ziano di, jsoc or / and u0433u0430u043bu043eu0433u0435u043du0437u0430u043cu0435u0449u0435u043du043du044bu0439 c1 - c6 - u0430u043bu043au0438u043b, for example, u044du0442u043eu043au0441u0438u043au0430u0440u0431u043eu043du0438u043b - or u0430u0440u0438u043b, n u0430u043fu0440u0438u043cu0435u0440, u0444u0435u043du0438u043b, a u0433u0430u043bu043eu0433u0435u043du0444u0435u043du0438u043b, u043du0430u0444u0442u0438u043b,;(ii) saturated or certainly unsaturated elaborate or u043du0435u0440u0430u0437u0432u0435u0442u0432u043bu0435u043du043du044bu0439 c1 - c6 - u0430u043bu043au043eu043au0441u0438 or;(iii) in particular, c1 - c6 - u0430u043bu043au0438u043b -, c1 - c3 u0430u043bu043au043eu043au0441u0438 -, hydroxyl -, u043au0430u0440u0431u043eu043au0441u0438u043b - sulfonyl -, nitro -, ziano di, jsoc or / and u0433u0430u043bu043eu0433u0435u043du0437u0430u043cu0435u0449u0435u043du043du044bu0439 u0444u0435u043du043eu043au0441u0438 or u0431u0435u043du0437u0438u043bu043eu043au0441u0438u043au0430u0440u0431u043eu043du0438u043b,;r2 denotes, in particular, c1 - c6 - u0430u043bu043au0438u043b -, c1 - c3 u0430u043bu043au043eu043au0441u0438 -, hydroxyl -, u043au0430u0440u0431u043eu043au0441u0438u043b - sulfonyl -, nitro -, ziano di, jsoc or / and u0433u0430u043bu043eu0433u0435u043du0437u0430u043cu0435u0449u0435u043du043du044bu0439 u0444u0435u043du0438u043bu044cu043du044bu0439 balance, for example, u0444u0435u043du0438u043b u043cu0435u0442u0438u043bu0444u0435u043du0438u043b, 4, 2, 4, 6 - u0442u0440u0438u043cu0435u0442u0438u043bu0444u0435u043du0438u043b, 2, 4, 6 - u0438u0437u043eu043fu0440u043eu043fu0438u043bu0444u0435u043du0438u043b, 4 - u043cu0435u0442u043eu043au0441u0438 - 2,3,6 - u0442u0440u0438u043cu0435u0442u0438u043bu0444u0435u043du0438u043b,;r3 is h or u043fu0440u0435u0434u0441u0442u0430u0432u043bu00a0u0435u0442 elaborate or u043du0435u0440u0430u0437u0432u0435u0442u0432u043bu0435u043du043du044bu0439 c1 - c4 - u0430u043bu043au0438u043b and;n denotes 0 or 1.;z represents n or CR9 where R9 u00a0u0432u043bu00a0u0435u0442u0441u00a0 n or u0440u0430u0437u0432u0435u0442u0432u043bu0435u043du043du044bu043c or u043du0435u0440u0430u0437u0432u0435u0442u0432u043bu0435u043du043du044bu043c c1 - c4 - u0430u043bu043au0438u043bu043eu043c.;4. way to a 3 - 1, in which u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du043eu043bu0430u043bu0430u043du0438u043du0430 u00a0u0432u043bu00a0u0435u0442u0441u00a0 derivative of n - (2, 4, 6 - u0442u0440u0438u0438u0437u043eu043fu0440u043eu043fu0438u043b - u0444u0435u043du0438u043bu0441u0443u043bu044cu0444u043eu043du0438u043b - 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043e - (d, l) - u0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430, or the l - u044du043du0430u043du0442u0438u043eu043cu0435u0440u043eu043c.;5. way to a 3 - 1, in which u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 u00a0u0432u043bu00a0u0435u0442u0441u00a0 n - TIPPS - 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043e - (d, l) - phenylalanine - 4 - u044du0442u043eu043au0441u0438u043au0430u0440u0431u043eu043du0438u043bu043fu0438u043fu0435u0440u0430u0437u0438u0434u043eu043c, or l - u044du043du0430u043du0442u0438u043eu043cu0435 rum.;6. method for 1, in which a phase (a) using the solution of the derivative 3 u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 in acetone.;7. method for 1, in which the residue on the stage (b) u043eu0442u0434u0435u043bu00a0u044eu0442 by filtration.;8. method for 1, in which u0440u0435u043au0443u043fu0435u0440u0430u0446u0438u00a0 stage (c) is generated by the reaction of NaHCO3.;9. method for 1, which receive a 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 with purity of more than 90%.;10. method for 1, which receive a 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 with purity of more than 95%.;11. method for 1, which receive a 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 with purity of more than 99%.;12. method u043fu043eu043bu0443u0447u0435u043du0438u00a0 derivatives of 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430, comprising the following steps: u0441u0435u0431u00a0;(i) u0440u0435u0430u043au0446u0438u00a0 exchange n - protected 3 u0446u0438u0430u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 with derivative u043fu0438u043fu0435u0440u0430u0437u0438u043du0430 education n - protected 3 u0446u0438u0430u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043d - u043fu0438u043fu0435u0440u0430u0437u0438u0434u0430,;(ii) u0440u0435u0430u043au0446u0438u00a0 exchange with, if necessary, u0437u0430u043cu0435u0449u0435u043du043du044bu043c u0444u0435u043du0438u043bu0441u0443u043bu044cu0444u043eu043du0438u043bu0433u0430u043bu043eu0433u0435u043du0438u0434u043eu043c;;(iii) the u0446u0438u0430u043du043eu0433u0440u0443u043fu043fu044b in u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0433u0440u0443u043fu043fu0443;(iv) purification of the derivative 3 u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 way on any of the u043fu043f.1 - 11.;13. way on p.12, which in phase (i) use derivative boc protected n - 3 - u0446u0438u0430u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430.;14. way on p.12, which derived u043fu0438u043fu0435u0440u0430u0437u0438u043du0430 in phase (i) u00a0u0432u043bu00a0u0435u0442u0441u00a0 u044du0442u043eu043au0441u0438u043au0430u0440u0431u043eu043du0438u043bu043fu0438u043fu0435u0440u0430u0437u0438u043du043eu043c.;15. way on p.12, in which phase (ii) is u0440u0435u0430u043au0446u0438u00a0 u0437u0430u043cu0435u0449u0435u043du0438u00a0 with 2, 4, 6 - u0442u0440u0438u0438u0437u043eu043fu0440u043eu043fu0438u043bu0431u0435u043du0437u043eu043bu0441u0443u043bu044cu0444u043eu043du0438u043bu0445u043bu043eu0440u0438u0434u043eu043c.;16. way on p.12, which u043fu0438u0430u043du043eu0433u0440u0443u043fu043fu0443 phase (iii) by u0433u0438u0434u0440u043eu0445u043bu043eu0440u0438u0434u0430 u0433u0438u0434u0440u043eu043au0441u0438u043bu0430u043cu0438u043du0430 in the presence of carbonate u043du0430u0442u0440u0438u00a0 or u0442u0440u0438u044du0442u0438u043bu0430u043cu0438u043du0430 make u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043d u043eu0433u0440u0443u043fu043fu0443.;17. way on p.12, which receive a 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 with purity of more than 90%.;18. way on p.12, which receive a 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 with purity of more than 95%.;19. way on p.7, which receive a 3 - u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 with purity of more than 99%.;20. method u043fu043eu043bu0443u0447u0435u043du0438u00a0 derivatives of 3 - u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430, comprising the following steps: u0441u0435u0431u00a0;(i) to obtain the derivative 3 u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0444u0435u043du0438u043bu0430u043bu0430u043du0438u043du0430 way on any of the u043fu043f.9 - 19, and;(ii) the u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0433u0440u0443u043fu043fu044b in u0430u043cu0438u0434u0438u043du043eu0433u0440u0443u043fu043fu0443.;21. way on p.20, which u0433u0438u0434u0440u043eu043au0441u0438u0430u043cu0438u0434u0438u043du043eu0433u0440u0443u043fu043fu0443 at stage (ii) by reaction of the u0430u0446u0435u0442u0430u043du0433u0438u0434u0440u0438u0434u043eu043c and subsequent catalytic u0433u0438u0434u0440u0438u0440u043eu0432u0430u043du0438u00a0 made u0430u043cu0438u0434u0438u043d u043eu0433u0440u0443u043fu043fu0443.