CN110183393B - Method for preparing linazolone intermediate - Google Patents
Method for preparing linazolone intermediate Download PDFInfo
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- CN110183393B CN110183393B CN201910637282.9A CN201910637282A CN110183393B CN 110183393 B CN110183393 B CN 110183393B CN 201910637282 A CN201910637282 A CN 201910637282A CN 110183393 B CN110183393 B CN 110183393B
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/89—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper combined with noble metals
- B01J23/892—Nickel and noble metals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
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Abstract
The invention provides a method for preparing a linezolid intermediate (S) -5- (aminomethyl) -3- (3-fluoro-4-morpholinyl phenyl) -2-oxazolidinone, which comprises the following steps: respectively adding ammonia water, basic nickel carbonate and a platinum-carbon or palladium-carbon catalyst into a reaction bottle, and stirring to obtain the catalyst; the weight ratio of the basic nickel carbonate to the ammonia water to the palladium carbon or the platinum carbon is 1: 1-10: 1-5; and (2) putting the compound 9 into an autoclave, adding the catalyst prepared in the step (1), introducing hydrogen while stirring, discharging pressure after the reaction is finished, filtering the reaction material to remove the catalyst, and concentrating and drying the filtrate to obtain a white solid. According to the invention, on the basis of palladium-carbon or platinum-carbon catalytic hydrogenation reaction, the basic nickel carbonate compound is added, so that the defluorination reaction is effectively inhibited, the product has high purity without refining, the high standard of the raw material medicine is reached, and the cost is effectively saved.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing a linazolone intermediate (S) -5- (aminomethyl) -3- (3-fluoro-4-morpholinyl phenyl) -2-oxazolidinone.
Background
The linazolidone (compound 1) is a chemically synthesized antibacterial drug, is used for treating bacteremia caused by vancomycin-resistant enterococci, pneumonia and comprehensive skin infection caused by methicillin-resistant staphylococcus aureus and bacteremia caused by penicillin-resistant streptococcus pneumoniae, has obvious effect and is widely applied to medicine.
There are many processes for synthesizing linazolone reported in the literature, and the following process is widely adopted because of the availability of raw materials, relatively low cost and easy industrial production.
In the research process, the inventor finds that when the compound 9 is subjected to catalytic hydrogenation to prepare 10 (with the chemical name of (S) -5- (aminomethyl) -3- (3-fluoro-4-morpholinylphenyl) -2-oxazolidinone), commercially available catalysts of Raney nickel, palladium carbon or platinum carbon are selected, defluorination products are generated, the structural formula is shown as 11, and the content is about 0.2-0.7%.
Although the amount of impurities is not large, the raw material medicine can be obtained by one-step reaction, the single impurity requirement is less than 0.1%, and the impurities have similar structures and properties with the intermediate 10, so that certain difficulty is brought to refining, and a high-purity product is difficult to obtain.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for preparing a high-purity linazolone intermediate.
The technical scheme for realizing the above purpose of the invention is as follows: a method for preparing a high purity linazolone intermediate comprising the steps of:
(1) preparing a catalyst, namely respectively adding ammonia water, basic nickel carbonate and a platinum-carbon or palladium-carbon catalyst into a reaction bottle and stirring; the weight ratio of the basic nickel carbonate to the ammonia water to the palladium carbon or the platinum carbon is 1: 1-10: 1-5;
(2) putting a compound 9 into an autoclave, adding the catalyst prepared in the step (1), introducing hydrogen, discharging pressure after the reaction is finished, filtering a reaction material to remove the catalyst, and concentrating and drying the filtrate to obtain a white solid; the specific reaction formula is as follows:
preferably, the weight ratio of the basic nickel carbonate, the ammonia water and the palladium carbon or the platinum carbon in the step (1) is 1: 3-5: 1-3.
Preferably, the mass concentration of the ammonia water in the step (1) is 10-28%.
Preferably, the solvent used in step (2) is methanol or ethanol.
Preferably, the weight ratio of the compound 9 to the solvent in the step (2) is 1: 3-10; furthermore, the weight ratio of the compound 9 to the solvent in the step (2) is 1: 3-6.
Preferably, the weight ratio of the compound 9 to the catalyst in the step (2) is 1: 0.05-1: 0.2.
Preferably, the reaction temperature in the step (2) is 20-60 ℃.
Preferably, the hydrogen pressure in the step (2) is 0.5-1.5 MPa; further, the hydrogen pressure in the step (2) is 0.5-1.0 MPa; furthermore, the hydrogen pressure in the step (2) is 0.5-0.8 MPa.
The invention has the following beneficial effects: according to the invention, on the basis of palladium-carbon or platinum-carbon catalytic hydrogenation reaction, the basic nickel carbonate compound is added, so that the defluorination reaction is effectively inhibited, the product has high purity without refining, the high standard of the raw material medicine is reached, and the cost is effectively saved.
Detailed Description
The present invention will be further specifically described below with reference to examples, but is not limited thereto.
EXAMPLE 1 preparation of the catalyst
30g of 10% ammonia water and 10g of basic nickel carbonate (2 NiCO) were placed in a 250ml glass reaction flask3.3Ni(OH)3.4H2O), stirring for 0.5h at room temperature, then adding 10g of 5% palladium carbon (water content 60%), stirring for 0.5h to obtain paste for later use.
30g of compound 9 (molecular weight of 321.3,93.4mmol),150g of methanol and 6g of the catalyst are put into a 500ml autoclave, a kettle cover is covered, air in the kettle is replaced by nitrogen for 3 times, then the replacement is carried out by hydrogen for 2 times, then the temperature is controlled to be 20-30 ℃ (the reaction is exothermic, cooling water is used for cooling), the reaction is carried out under the condition of maintaining the hydrogen pressure in the kettle at 0.6MPa, sampling and central control are carried out for 6 hours, the reaction of the raw materials is finished, the pressure is removed, the catalyst is removed by filtering a reaction material, the filtrate is decompressed and distilled to recover the methanol to be dry, 27.0g of white solid is obtained, the chromatographic purity is 99.9%, the defluorinated impurity is 0.03%, and the yield is 97.8%.
1H NMR(DMSO-d6)δppm:7.51(m,1H),7.20(m,1H),7.05(t,1H),4.59(m,1H),3.92(m,2H),3.73(m,4H),2.95(m,4H),2.80(m,2H),1.63(s,2H)。
Example 2
50g of 10% ammonia water and 10g of basic nickel carbonate (2 NiCO) were placed in a 250ml glass reaction flask3.3Ni(OH)3.4H2O), stirring for 0.5h at room temperature, then adding 30g of 5% palladium carbon (water content 60%), stirring for 0.5h to obtain paste for later use.
30g of compound 9 (molecular weight: 321.3,93.4mmol), 90g of ethanol and 1.5g of the catalyst are put into a 500ml autoclave, a kettle cover is covered, air in the kettle is replaced by nitrogen for 3 times, then the replacement is carried out by hydrogen for 2 times, then the temperature is controlled to be 30-40 ℃ (the reaction releases heat, cooling water is cooled), the reaction is carried out under the condition that the hydrogen pressure in the kettle is maintained at 0.8MPa, sampling is carried out for 5 hours, the control is carried out during the middle reaction of the raw materials, the pressure is removed, the reaction materials are filtered to remove the catalyst, the filtrate is decompressed and distilled to recover ethanol to be dry, 26.8g of white solid is obtained, the chromatographic purity is 99.9%, the defluorinated impurity is 0.03%, and the yield is 97.1%.
Example 3
30g of 10% ammonia water and 10g of basic nickel carbonate (2 NiCO) were placed in a 250ml glass reaction flask3.3Ni(OH)3.4H2O), stirring for 0.5h at room temperature, then adding 20g of 5% palladium carbon (water content 60%), stirring for 0.5h to obtain paste for later use.
30g of compound 9 (molecular weight: 321.3,93.4mmol), 180g of methanol and 2g of the catalyst are put into a 500ml autoclave, a kettle cover is covered, air in the kettle is replaced by nitrogen for 3 times, then hydrogen is replaced for 2 times, then the temperature is controlled to be 40-60 ℃ (the reaction is exothermic, cooling water is used for cooling), the reaction is carried out under the condition that the hydrogen pressure in the kettle is maintained at 0.5MPa, sampling is carried out for 3 hours, the control is carried out, the reaction is finished after the reaction of the raw materials, the pressure is removed, the catalyst is removed by filtering reaction materials, the filtrate is subjected to reduced pressure distillation to recover the methanol to be dry, 27.1g of white solid is obtained, the chromatographic purity is 99.8%, the defluorinated impurity is 0.06%, and the yield is 98.0%.
Comparative example:
30g of compound 9,150 g of methanol and 3 g of 5% palladium carbon catalyst (with water content of 60%) are put into a 500ml high-pressure kettle, a kettle cover is covered, air in the kettle is replaced by nitrogen for 3 times and then replaced by hydrogen for 2 times, then the temperature is controlled to be 30-40 ℃ (the reaction is exothermic and cooled by cooling water), the pressure of the hydrogen in the kettle is maintained to be 0.7MPa for reaction, sampling and controlling are carried out for 6 hours, the pressure is removed after the reaction of the raw materials is finished, the catalyst is removed by filtering reaction materials, the filtrate is decompressed and distilled to recover the methanol to be dry, 26.8g of white solid is obtained, the chromatographic purity is 99.2%, the defluorinated impurity is 0.5%, and the yield is 96.0%.
The catalyst only uses common palladium carbon, and basic nickel carbonate inhibitor is not added, so defluorination impurities are obviously increased.
The products of the above examples were confirmed by nuclear magnetic and mass spectrometry.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference.
Claims (8)
1. A process for preparing a linezolid intermediate comprising the steps of:
(1) preparing a catalyst, namely respectively adding ammonia water, basic nickel carbonate and a platinum-carbon or palladium-carbon catalyst into a reaction bottle and stirring; the weight ratio of the basic nickel carbonate to the ammonia water to the palladium carbon or the platinum carbon is 1: 1-10: 1-5;
(2) adding a compound 9 into an autoclave, adding the catalyst prepared in the step (1), introducing hydrogen while stirring, discharging pressure after the reaction is finished, filtering a reaction material to remove the catalyst, and concentrating and drying the filtrate to obtain a white solid; the specific reaction formula is as follows:
2. the method for preparing the linazolone intermediate, according to claim 1, is characterized in that the weight ratio of the basic nickel carbonate, the ammonia water and the palladium carbon or the platinum carbon in the step (1) is 1: 3-5: 1-3.
3. The method for preparing a linezolid intermediate according to claim 1, wherein the solvent used in step (2) is methanol or ethanol.
4. The method for preparing the linazolone intermediate as claimed in claim 1, wherein the weight ratio of the compound 9 to the solvent in the step (2) is 1: 3-10.
5. The method for preparing the linazolone intermediate as claimed in claim 1, wherein the weight ratio of the compound 9 to the catalyst in the step (2) is 1: 0.05-1: 0.2.
6. The method for preparing the linazolone intermediate as claimed in claim 1, wherein the reaction temperature in the step (2) is 20-60 ℃.
7. The method for preparing the linezolid intermediate according to claim 1, wherein the hydrogen pressure in step (2) is 0.5 to 1.5 MPa.
8. The method for preparing a linezolid intermediate according to claim 7, wherein the hydrogen pressure in step (2) is 0.5 to 1.0 MPa.
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| CN201910637282.9A CN110183393B (en) | 2019-07-15 | 2019-07-15 | Method for preparing linazolone intermediate |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102898375A (en) * | 2012-11-13 | 2013-01-30 | 齐鲁动物保健品有限公司 | Preparation method of 2-(3-aminophenyl) imidazoline hydrochloride |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102898375A (en) * | 2012-11-13 | 2013-01-30 | 齐鲁动物保健品有限公司 | Preparation method of 2-(3-aminophenyl) imidazoline hydrochloride |
Non-Patent Citations (1)
| Title |
|---|
| 利奈唑胺中间体的制备工艺优化;罗海荣等;《山东化工》;20181231;第47卷(第12期);1-2 * |
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