IES86990B2 - Drugs intermediates 1,4-dibromo-2,3-butanediol synthesis method - Google Patents
Drugs intermediates 1,4-dibromo-2,3-butanediol synthesis method Download PDFInfo
- Publication number
- IES86990B2 IES86990B2 IES20180085A IES20180085A IES86990B2 IE S86990 B2 IES86990 B2 IE S86990B2 IE S20180085 A IES20180085 A IE S20180085A IE S20180085 A IES20180085 A IE S20180085A IE S86990 B2 IES86990 B2 IE S86990B2
- Authority
- IE
- Ireland
- Prior art keywords
- solution
- mol
- dibromo
- mass fraction
- butanediol
- Prior art date
Links
- 239000000543 intermediate Substances 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 title claims abstract description 9
- 229940079593 drug Drugs 0.000 title claims abstract description 9
- 238000001308 synthesis method Methods 0.000 title claims abstract description 8
- XOWDQAHYPSENAC-UHFFFAOYSA-N 1,4-dibromobutane-2,3-diol Chemical compound BrCC(O)C(O)CBr XOWDQAHYPSENAC-UHFFFAOYSA-N 0.000 title claims abstract description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 16
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 239000007787 solid Substances 0.000 claims abstract description 9
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012024 dehydrating agents Substances 0.000 claims abstract description 8
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims abstract description 8
- 150000002825 nitriles Chemical class 0.000 claims abstract description 8
- 239000000047 product Substances 0.000 claims abstract description 7
- QIODANQULLIVBX-UHFFFAOYSA-N 1,4-diaminobutane-2,3-dione Chemical compound NCC(=O)C(=O)CN QIODANQULLIVBX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229940036348 bismuth carbonate Drugs 0.000 claims abstract description 6
- 239000013078 crystal Substances 0.000 claims abstract description 6
- GMZOPRQQINFLPQ-UHFFFAOYSA-H dibismuth;tricarbonate Chemical compound [Bi+3].[Bi+3].[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O GMZOPRQQINFLPQ-UHFFFAOYSA-H 0.000 claims abstract description 6
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 238000010189 synthetic method Methods 0.000 description 2
- IFTGEZOPUAJVMG-UHFFFAOYSA-N 1,1-dibromobut-1-ene Chemical compound CCC=C(Br)Br IFTGEZOPUAJVMG-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/64—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by simultaneous introduction of -OH groups and halogens
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Drugs intermediates 1,4-dibromo-2,3-butanediol synthesis method, comprises the following steps: the reaction vessel was added 2 mol 1,4-diaminobutanedione, 4-6 mol 2-pyrrolidone, the solution temperature was reduced to 5-7 V, then followed by the addition of 2-3 mol basic bismuth carbonate and 4-6 mol hydrogen bromide solution for 30-60 min, continued to reduce the temperature to 1-3 V, controlled the stirring speed at 170-190 rpm, kept for 40-60 min, standing for 30-50 mm, precipitated the solids, the filtrate was washed with butyric acid methyl ester solution and the nitrile solution, recrystallized from the cyclohexanone solution to precipitate the crystals and the dehydrated with dehydrating agent, obtained the finished product 1,4-dibromo-2,3-butanediol.
Description
FIELD OF THE INVENTION
The present invention relates to drugs intermediates l,4-dibromo-2,3-butanediol synthesis method.
GENERAL BACKGROUND
I,4-dibromo-2,3-butanediol is mainly used as a drug intermediate. However, most of the existing synthetic methods are using dibromobutene as the reactant, it is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthetic method for further improving the quality and yield of the product and reducing the byproduct content, it has important economic significance.
SUMMARY
The purpose of the present invention is to provide drugs intermediates
1.4- dibromo-2,3-butanediol synthesis method, comprises the following steps:
(i) The reaction vessel was added 2 mol 1,4-diaminobutanedione, 4-6 mol 2-pyrrolidone, the solution temperature was reduced to 5-7 °C, then followed by the addition of 2-3 mol basic bismuth carbonate and 4-6 mol hydrogen bromide solution for 30-60 min, continued to reduce the temperature to 1-3 °C, controlled the stirring speed at 170-190 rpm, kept for 40-60 min, standing for 30-50 min, precipitated the solids, the filtrate was washed with butyric acid methyl ester solution and the nitrile solution, recrystallized from the cyclohexanone solution to precipitate the crystals and the dehydrated with dehydrating agent, obtained the finished product
1.4- dibromo-2,3-butanediol; wherein, the mass fraction of the hydrogen bromide solution in step (i) is 15 to 20%, the mass fraction of the butyric acid methyl ester solution in step (i) is 60 to 66% and the mass fraction of the nitrile solution described in step (i) is 75 to 83%, the mass fraction of cyclohexanone solution in step (i) is 90-96%, and the dehydrating agent described in step (i) is any one of anhydrous potassium carbonate and solid sodium hydroxide.
Throughout the reaction process can be the following reaction formula:
Br^.
RifoCH2
CH2|
I^oh ΟΆ\4 C.,H?NO - (BiOKOvl/2H2O ’ HBr--► H° T
IH,C
HjC^ ^Br
NH2
Advantage of the present invention is that: reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
drugs intermediates 1,4-dibromo-2,3-butanediol synthesis method.
Embodiment I
The reaction vessel was added 2 mol 1,4-diaminobutanedione, 4 mol 2-pyrrolidone, the solution temperature was reduced to 5 °C, then followed by the addition of 2 mol basic bismuth carbonate and 4 mol hydrogen bromide solution with a 15 mass fraction of 15% for 30min, continued to reduce the temperature to 1 C, controlled the stirring speed at 170 rpm, kept for 40 min, standing for 30 min, precipitated the solids, the filtrate was washed with butyric acid methyl ester solution with a mass fraction of 60% and the nitrile solution with a mass fraction of 75%, recrystallized from the cyclohexanone solution with a mass fraction of 90% to 20 precipitate the crystals and the dehydrated with anhydrous potassium carbonate dehydrating agent, obtained the finished product l,4-dibromo-2,3-butanediol 446.4g, yield of 90%.
Embodiment 2
The reaction vessel was added 2 mol 1,4-diaminobutanedione, 5 mol
2-pyrrolidone, the solution temperature was reduced to 6 “C, then followed by the addition of 2.5 mol basic bismuth carbonate and 5 mol hydrogen bromide solution with a mass fraction of 17% for 40min, continued to reduce the temperature to 2 C, controlled the stirring speed at 180 rpm, kept for 50 min, standing for 40 min, precipitated the solids, the filtrate was washed with butyric acid methyl ester solution with a mass fraction of 63% and the nitrile solution with a mass fraction of 80%, recrystallized from the cyclohexanone solution with a mass fraction of 93% to precipitate the crystals and the dehydrated with solid sodium hydroxide dehydrating agent, obtained the finished product l,4-dibromo-2,3-butanediol 456.32g, yield of 92%.
Embodiment 3
The reaction vessel was added 2 mol 1,4-diaminobutanedione, 6 mol
2-pyrrolidone, the solution temperature was reduced to 7 °C, then followed by the addition of 3 mol basic bismuth carbonate and 6 mol hydrogen bromide solution with a mass fraction of 20% for 60min, continued to reduce the temperature to 3 °C, 15 controlled the stirring speed at 190 rpm, kept for 60 min, standing for 50 min, precipitated the solids, the filtrate was washed with butyric acid methyl ester solution with a mass fraction of 66% and the nitrile solution with a mass fraction of 83%, recrystallized from the cyclohexanone solution with a mass fraction of 96% to precipitate the crystals and the dehydrated with anhydrous potassium carbonate 20 dehydrating agent, obtained the finished product l,4-dibromo-2,3-butanediol 471.2g, yield of 95%.
Claims (3)
1. Drugs intermediates l,4-dibromo-2,3-butanediol synthesis method, comprises the following steps: (i) The reaction vessel was added 2 mol 1,4-diaminobutanedione, 4-6 mol 5 2-pyrrolidone, the solution temperature was reduced to 5-7 °C, then followed by the addition of 2-3 mol basic bismuth carbonate and 4-6 mol hydrogen bromide solution for 30-60 min, continued to reduce the temperature to 1-3 °C, controlled the stirring speed at 170-190 rpm, kept for 40-60 min, standing for 30-50 min, precipitated the solids, the filtrate was washed with butyric acid methyl ester solution and the nitrile 10 solution, recrystallized from the cyclohexanone solution to precipitate the crystals and the dehydrated with dehydrating agent, obtained the finished product 1,4-dibromo-2,3-butanediol; wherein, the mass fraction of the hydrogen bromide solution in step (i) is 15 to 20%, the mass fraction of the butyric acid methyl ester solution in step (i) is 60 to 66% and the mass fraction of the nitrile solution described 15 in step (i) is 75 to 83%.
2. Drugs intermediates l,4-dibromo-2,3-butanediol synthesis method according to claim 1 wherein the mass fraction of cyclohexanone solution in step (i) is 90-96%. 20
3. Drugs intermediates l,4-dibromo-2,3-butanediol synthesis method according to claim 1 wherein the dehydrating agent described in step (i) is any one of anhydrous potassium carbonate and solid sodium hydroxide.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710216098.8A CN108238847A (en) | 2017-04-05 | 2017-04-05 | A kind of synthetic method of bis- bromo- 2,3- butanediols of pharmaceutical intermediate 1,4- |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES20180085A2 IES20180085A2 (en) | 2019-04-03 |
| IES86990B2 true IES86990B2 (en) | 2019-05-01 |
Family
ID=58744599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IES20180085A IES86990B2 (en) | 2017-04-05 | 2018-03-27 | Drugs intermediates 1,4-dibromo-2,3-butanediol synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238847A (en) |
| AU (1) | AU2018100415A4 (en) |
| GB (1) | GB201705845D0 (en) |
| IE (1) | IES86990B2 (en) |
-
2017
- 2017-04-05 CN CN201710216098.8A patent/CN108238847A/en active Pending
- 2017-04-11 GB GBGB1705845.4A patent/GB201705845D0/en not_active Ceased
-
2018
- 2018-03-27 IE IES20180085A patent/IES86990B2/en unknown
- 2018-04-01 AU AU2018100415A patent/AU2018100415A4/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| GB201705845D0 (en) | 2017-05-24 |
| IES20180085A2 (en) | 2019-04-03 |
| AU2018100415A4 (en) | 2018-05-10 |
| CN108238847A (en) | 2018-07-03 |
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