CN102464604A - Production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one - Google Patents
Production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one Download PDFInfo
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- CN102464604A CN102464604A CN2010105352954A CN201010535295A CN102464604A CN 102464604 A CN102464604 A CN 102464604A CN 2010105352954 A CN2010105352954 A CN 2010105352954A CN 201010535295 A CN201010535295 A CN 201010535295A CN 102464604 A CN102464604 A CN 102464604A
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- carbazolone
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Abstract
A production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one. The 1,2,3,4-tetrahydro-9-methylcarbazol-4-one product is prepared by recrystallization of acetone by using a raw material of 1,2,3,9-tetrahydro-4H-carbazol-4-one and a methylation reagent of dimethyl carbonate. The production route of the invention is short, low-cost, safe and environment-friendly during production, and has high product yield and purity.
Description
Technical field
The present invention relates to a kind of working method from the synthetic N-methyl tetrahydro-carbazolone of tetrahydro-carbazolone.
Background technology
N-methyl tetrahydro-carbazolone (1,2,3,4-Tetrahydro-9-methylcarbazol-4-one), have another name called 1,2,3,4-tetrahydrochysene-9-methyl carbazole-4-ketone; 1,2,3,4-tetrahydrochysene-9-methyl-4H-carbazole ketone; The 9-methyl isophthalic acid, 2,3, the 4-tetrahydro-carbazolone; 1,2,3,4-tetrahydrochysene-9-methyl-4H-carbazole ketone, chemical structure is following:
N-methyl tetrahydro-carbazolone is the important midbody of 5-hydroxytryptamine receptor antagonist ondansetron (Ondansetron) of synthetic highly selective; Mainly prepare with tetrahydro-carbazolone generation methylation reaction at present with methyl-sulfate, methyl halide etc.; Methylating reagents such as used methyl-sulfate, methyl halide severe toxicity is very big to human health damage in the production process.Methylcarbonate is a kind of " green " chemical, and is nontoxic basically, can be miscible with most organism, registers as non-toxicant in Europe in 1992, contains methyl in its molecular structure, can be used as the substitute of methyl-sulfate, methyl halide.Utilize methylcarbonate to synthesize N-methyl tetrahydro-carbazolone, improved security, the feature of environmental protection of building-up process greatly.
Summary of the invention
The object of the present invention is to provide a kind of production process safety, environmental protection, and operational path is simple, the N-methyl tetrahydro-carbazolone working method of easy purification of products.
In order to achieve the above object; The technical scheme that the present invention adopts is that tetrahydro-carbazolone is dissolved in a kind of organic solvent; Add a kind of mineral alkali and methylcarbonate successively, stirred 6～12 hours down, after reaction finishes at 100～150 ℃; Naturally cooling gets N-methyl tetrahydro-carbazolone through underpressure distillation, washing, drying, acetone recrystallization.
Advantage of the present invention is:
1. the present invention is a raw material with the tetrahydro-carbazolone, is methylating reagent with the methylcarbonate, used organic solvent low toxicity, the safety of building-up process, environmental protection.
2. operational path of the present invention is short, and treatment process is simple, and purifying products is easy.
Embodiment
Describe in further detail below in conjunction with embodiments of the invention:
1. the working method of a N-methyl tetrahydro-carbazolone is dissolved in tetrahydro-carbazolone in a kind of organic solvent, adds a kind of mineral alkali and methylcarbonate successively; Stirred 6～12 hours down at 100～150 ℃, after reaction finishes, naturally cooling; Get N-methyl tetrahydro-carbazolone product through underpressure distillation, washing, drying, acetone recrystallization, the mol ratio of described tetrahydro-carbazolone and mineral alkali is 1: 1.0～1.5, and the mol ratio of described tetrahydro-carbazolone and methylcarbonate is 1: 2.0～4.5; 10～20 milliliters/gram 1 of described consumption of organic solvent; 2,3, the 9-tetrahydro-carbazolone.
2. used organic solvent is N, dinethylformamide or DMSO 99.8MIN..
3. used mineral alkali is Pottasium Hydroxide or sodium hydroxide.
Embodiment 1
18.5 gram (0.1mol) tetrahydro-carbazolones are dissolved in 185 milliliters of N, in the dinethylformamide, under agitation add 5.6 gram (0.1mol) Pottasium Hydroxide, 18.0 gram (0.2mol) methylcarbonates successively; Stirred 6 hours down at 100 ℃; After reaction finished, naturally cooling got 13.0 gram N-methyl tetrahydro-carbazolones through underpressure distillation, washing, drying, acetone recrystallization; Purity 97.0%, yield 63.4%.
Embodiment 2
18.5 gram (0.1mol) tetrahydro-carbazolones are dissolved in 370 milliliters of DMSO 99.8MIN.s; Under agitation add 6.0 gram (0.15mol) sodium hydroxide, 40.5 gram (0.45mol) methylcarbonates successively, stirred 12 hours down at 150 ℃, after reaction finishes; Naturally cooling; Get 14.2 gram N-methyl tetrahydro-carbazolones, purity 95.0%, yield 67.8% through underpressure distillation, washing, drying, acetone recrystallization.
Embodiment 3
18.5 gram (0.1mol) tetrahydro-carbazolones are dissolved in 250 milliliters of N, in the dinethylformamide, under agitation add 6.5 gram (0.12mol) Pottasium Hydroxide, 27.0 gram (0.3mol) methylcarbonates successively; Stirred 8 hours down at 140 ℃; After reaction finished, naturally cooling got 14.3 gram N-methyl tetrahydro-carbazolones through underpressure distillation, washing, drying, acetone recrystallization; Purity 96.5%, yield 69.3%.
Claims (3)
1. the working method of a N-methyl tetrahydro-carbazolone; It is characterized in that: tetrahydro-carbazolone is dissolved in a kind of organic solvent, adds a kind of mineral alkali and methylcarbonate successively, stirred 6～12 hours down at 100～150 ℃; After reaction finishes; Naturally cooling gets N-methyl tetrahydro-carbazolone product through underpressure distillation, washing, drying, acetone recrystallization, and the mol ratio of described tetrahydro-carbazolone and mineral alkali is 1: 1: 1.0～1.5; The mol ratio of described tetrahydro-carbazolone and methylcarbonate is 1: 2.0～4.5, and described consumption of organic solvent is 10～20 a milliliters/gram tetrahydro-carbazolone.
2. according to the working method of the described N-methyl of claim 1 tetrahydro-carbazolone, it is characterized in that: used organic solvent is N, dinethylformamide or DMSO 99.8MIN..
3. according to the working method of the described N-methyl of claim 1 tetrahydro-carbazolone, it is characterized in that: used mineral alkali is Pottasium Hydroxide or sodium hydroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105352954A CN102464604A (en) | 2010-11-09 | 2010-11-09 | Production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105352954A CN102464604A (en) | 2010-11-09 | 2010-11-09 | Production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one |
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| CN102464604A true CN102464604A (en) | 2012-05-23 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2010105352954A Pending CN102464604A (en) | 2010-11-09 | 2010-11-09 | Production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115677561A (en) * | 2022-11-01 | 2023-02-03 | 常州兰陵制药有限公司 | 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof |
| CN115677560A (en) * | 2022-11-01 | 2023-02-03 | 常州兰陵制药有限公司 | Synthesis method of 1,2,3, 9-tetrahydro-9-methyl-4H-carbazole-4-ketone |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101260045A (en) * | 2007-03-07 | 2008-09-10 | 抚顺市化工研究设计院 | Mono-methylation method for amines compounds |
-
2010
- 2010-11-09 CN CN2010105352954A patent/CN102464604A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101260045A (en) * | 2007-03-07 | 2008-09-10 | 抚顺市化工研究设计院 | Mono-methylation method for amines compounds |
Non-Patent Citations (1)
| Title |
|---|
| 匡永清等.: "《1,2,3,9-四氢-9-甲基-4H-咔唑-4-酮的合成》", 《中国医药工业杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115677561A (en) * | 2022-11-01 | 2023-02-03 | 常州兰陵制药有限公司 | 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof |
| CN115677560A (en) * | 2022-11-01 | 2023-02-03 | 常州兰陵制药有限公司 | Synthesis method of 1,2,3, 9-tetrahydro-9-methyl-4H-carbazole-4-ketone |
| CN115677560B (en) * | 2022-11-01 | 2024-04-05 | 常州兰陵制药有限公司 | Synthesis method of 1,2,3, 9-tetrahydro-9-methyl-4H-carbazole-4-one |
| CN115677561B (en) * | 2022-11-01 | 2024-04-05 | 常州兰陵制药有限公司 | 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof |
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Application publication date: 20120523 |