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CN-122010827-A - Purification process method of 2-bromo-6-methoxypyridine

CN122010827ACN 122010827 ACN122010827 ACN 122010827ACN-122010827-A

Abstract

The invention discloses a purification process of 2-bromo-6-methoxypyridine, and belongs to the technical field of chemical pharmacy. The process comprises the steps of synthesis reaction and two-stage rectification, namely, firstly, reacting methanol, sodium hydroxide and 2, 6-dibromopyridine to obtain a mixture, then separating the mixture by a first rectifying tower at the normal pressure and the temperature of 300-310 ℃ to enable the 2-bromo-6-methoxypyridine to be distilled as a light component, and then refining the light component by a second rectifying tower at the normal pressure and the temperature of 200-210 ℃ to obtain a high-purity product. By optimizing parameters such as the number of feeding tower plates, the reflux ratio and the like, the purity of the product can reach more than 99%, the yield is about 92%, and the process is short and efficient and is suitable for industrial production.

Inventors

  • JIA PENG
  • ZHANG QI
  • LIU HONGJING
  • WANG KAI
  • ZHANG YING
  • ZHAO BIN
  • CUI LING

Assignees

  • 沈阳工业大学

Dates

Publication Date
20260512
Application Date
20251231

Claims (6)

  1. 1. The purification process of the 2-bromo-6-methoxypyridine is characterized by comprising the following steps of: (1) The first-stage rectification separation, namely introducing a mixture containing 2-bromo-6-methoxypyridine and 2, 6-dibromopyridine after reaction into a first rectification tower to be separated, wherein the 2-bromo-6-methoxypyridine is distilled out of the top of the tower as a light component, and the 2, 6-dibromopyridine is discharged from a tower kettle as a heavy component, the operation pressure of the first rectification tower is normal pressure, and the temperature of the tower kettle is 300-310 ℃; (2) And (2) secondary rectifying refining, namely introducing the tower top distillate obtained in the step (1) into a second rectifying tower for refining, wherein 2-bromo-6-methoxypyridine is taken as a heavy component and discharged from a tower kettle, and the high-purity 2-bromo-6-methoxypyridine product is obtained, the operating pressure of the second rectifying tower is normal pressure, and the temperature of the tower kettle is 200-210 ℃.
  2. 2. The process for purifying 2-bromo-6-methoxypyridine according to claim 1, further comprising, before step (1), a synthetic reaction step of charging methanol, sodium hydroxide and 2, 6-dibromopyridine into a reaction vessel, and reacting at 80-90 ℃ under normal pressure for 5-7 hours to obtain the post-reaction mixture containing 2-bromo-6-methoxypyridine and 2, 6-dibromopyridine.
  3. 3. The process for purifying 2-bromo-6-methoxypyridine according to claim 2, wherein in the synthesis reaction step, the molar ratio of methanol, sodium hydroxide to 2, 6-dibromopyridine is (1.2-1.3): 1.2-1.3.
  4. 4. The process for purifying 2-bromo-6-methoxypyridine according to claim 1, wherein in step (1), the first rectifying column has a feed tray number of 4 to 13 trays and a reflux ratio of 1.6 to 3.4.
  5. 5. The process for purifying 2-bromo-6-methoxypyridine according to claim 1, wherein in step (2), the second rectifying column has a feed tray number of 4 to 11 trays and a reflux ratio of 1.4 to 2.2.
  6. 6. A high purity 2-bromo-6-methoxypyridine product, characterized in that it is produced by the purification process of any one of claims 1 to 5 and has a purity of 99% or more.

Description

Purification process method of 2-bromo-6-methoxypyridine Technical Field The invention belongs to the technical field of chemical pharmaceutical preparation, and particularly relates to a purification process method of 2-bromo-6-methoxypyridine. Background With the development of the medical research industry in China, the purity requirements on various medical chemicals are gradually improved. 2-bromo-6-methoxypyridine has been widely used as a heterocyclic aromatic product for the preparation of various pharmaceutical products due to its excellent chemical structure, and its purity has an important influence on the yield of the pharmaceutical product. Aiming at the purification process of 2-bromo-6-methoxypyridine, no report on industrialization is found, and the purification process designs an industrialized purification scheme for the first time, and the purity can reach more than 99%. Disclosure of Invention Aiming at the defects existing in the prior art, the invention aims to provide a purification process method of 2-bromo-6-methoxypyridine to improve the yield of medicines, and the process has the characteristics of short process flow, high product purity and good quality. The technical scheme adopted by the invention is that the purification process method of the 2-bromo-6-methoxypyridine is characterized by comprising the following steps: (1) And (3) primary rectifying separation, namely introducing the reacted mixture containing 2-bromo-6-methoxypyridine and 2, 6-dibromopyridine into a first rectifying tower to be separated, wherein the 2-bromo-6-methoxypyridine is distilled out of the top of the tower as a light component, the 2, 6-dibromopyridine is discharged from a tower kettle as a heavy component, the operating pressure of the first rectifying tower is normal pressure, and the temperature of the tower kettle is 300-310 ℃. (2) And (2) secondary rectifying refining, namely introducing the tower top distillate obtained in the step (1) into a second rectifying tower for refining, wherein 2-bromo-6-methoxypyridine is taken as a heavy component and discharged from a tower kettle, and the high-purity 2-bromo-6-methoxypyridine product is obtained, the operating pressure of the second rectifying tower is normal pressure, and the temperature of the tower kettle is 200-220 ℃. In the scheme, before the step (1), the method further comprises a synthetic reaction step of putting methanol, sodium hydroxide and 2, 6-dibromopyridine into a reaction kettle, and reacting for 5-7 hours at 80-90 ℃ and normal pressure to obtain the reacted mixture containing 2-bromo-6-methoxypyridine and 2, 6-dibromopyridine. In the scheme, in the synthetic reaction step, the feeding mole ratio of methanol, sodium hydroxide and 2, 6-dibromopyridine is (1.2-1.3): 1. In the scheme, in the step (1), the feeding tower plate number of the first rectifying tower is 4-13 tower plates, and the reflux ratio is 1.6-3.4. In the scheme, in the step (2), the feeding tower plate number of the second rectifying tower is 4-11 tower plates, and the reflux ratio is 1.4-2.2. A high-purity 2-bromo-6-methoxypyridine product, which is prepared by the purification process according to any one of claims 1 to 5, and has a purity of 99% or more. The purification process method of the 2-bromo-6-methoxypyridine has the beneficial effects that a complete and industrialized purification scheme of the 2-bromo-6-methoxypyridine is designed for the first time, and the industrialized problem of high-purity preparation of the product is solved. The purity of the 2-bromo-6-methoxypyridine product is improved by carrying out primary separation and secondary refining on the product produced in the product reaction kettle, the target product is extracted by the original purification process through chlorine dioxide, and the product purity of the original process can reach 97% at most by carrying out distillation operation through a distillation tower after extraction. The patent provides a more efficient process, which improves the purity of the product by more than 99 percent. Drawings In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art. FIG. 1 is a flow chart of a process for purifying 2-bromo-6-methoxypyridine of the present invention; The serial numbers of the figures are as follows, 1a reaction kettle, 11 a reaction kettle feeding pipe, 12 a reaction kettle discharging pipe, 2a first rectifying tower, 21 a first rectifying tower ejection pipe, 22 a first rectifying tower kettle discharging pipe, 3a second rectifying tower, 31 a second rectifying tower ejection pipe and 32 a second