CN102702183A - New synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds - Google Patents
New synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds Download PDFInfo
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- CN102702183A CN102702183A CN2012101533911A CN201210153391A CN102702183A CN 102702183 A CN102702183 A CN 102702183A CN 2012101533911 A CN2012101533911 A CN 2012101533911A CN 201210153391 A CN201210153391 A CN 201210153391A CN 102702183 A CN102702183 A CN 102702183A
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- ester compounds
- butyl ester
- piperidines
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- propyl
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Abstract
The invention discloses a new synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds, effectively solving the disadvantages of the previously reported process, such as troublesome aftertreatment, high cost and relatively low yield. The new two-step reaction synthesis process comprises the steps of reacting material cyano group with hydroxyamino, and directly reacting with acid through a one-pot method. The whole process is easy to operate, the aftertreatment is simple, and the yield is greatly improved.
Description
Technical field
The present invention relates to 3-sec.-propyl-(new synthetic process of 1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds, genus medicine, chemical technology field.
Background technology
Sec.-propyl-(1; 2; 4) oxadiazole-5-piperidines-1-carbonyl tert-butyl ester compounds is important chemical intermediate, is widely used in medicine and pesticide field, and the synthetic route that is seen in report at present mostly is that raw material cyanic acid reacts with oxyammonia earlier; Obtain title product with sour condensation post-heating dehydration again, concrete route is following:
Above-mentioned route needs first condensation reaction to become after the amide-treated dehydration ring closure again, exists aftertreatment loaded down with trivial details, and cost is high, yield is on the low side wait not enough.
Summary of the invention
The present invention is directed to that the 3-sec.-propyl-(1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds compound method aftertreatment in the past is loaded down with trivial details; Cost is high; Yield is on the low side wait not enough, invented described with raw material cyanic acid and oxyammonia reaction back directly with sour one kettle way completion two-step reaction, make whole process easy handling; Aftertreatment is simple, and yield improves greatly.
Described 3-sec.-propyl-(1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic, and raw material cyanic acid class includes but are not limited to acetonitrile, positive propionitrile, and different third is fine, uncle's butyronitrile, isopropyl cyanide, n-Butyronitrile, positive valeronitrile, isovaleronitrile, nitrile-hexyl or the like.
Described 3-sec.-propyl-(1,2,4) oxadiazole-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic, and the raw material acids includes but are not limited to the 4-carbonyl tert-butyl ester-1 formic acid, acetate, propionic acid, cyclopropionate, butanic acid, ring butyric acid, chaulmoogric acid etc.
Said 3-sec.-propyl-(1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic, is comprised by (2) and (3) one pot reaction solution but is not limited only to toluene, YLENE, benzene, dioxane, 1,2-ethylene dichloride etc.
Said 3-sec.-propyl-(1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic to be comprised by (2) and (3) one pot reaction temperature but is not limited only to 0 degree centigrade to 200 degrees centigrade.
Said 3-sec.-propyl-(1,2,4) oxadiazole-5-piperidines-1-carbonyl tert-butyl ester compounds synthesizes one kettle way, purifying not midway, last Unified Treatment.
Above-mentioned is that the chemical reaction route of starting raw material is following with cyanic acid:
Embodiment
Preparation compound (2):
Starting raw material (1) 138 gram (2 moles) is dissolved in 1.4 liters of anhydrous methanols, adds oxammonium hydrochloride 152 grams (2.2 moles), under the frozen water cooling, adds 88 gram (2.2 moles) sodium hydroxide in batches; Add the back stirred overnight at room temperature, boil off methyl alcohol, residual solution is poured in 1 liter of frozen water; ETHYLE ACETATE (500 milliliters of * 4) layering extraction, saturated brine (500 milliliters) is washed anhydrous sodium sulfate drying; Filter, revolve driedly, obtain white solid 173 grams (yield 85%).
One kettle way prepares compound (5):
Freshly prepd compound (2) 102 grams (1 mole) are dissolved in 1 liter of toluene solution; Add the 4-carbonyl tert-butyl ester-1-nipecotic acid 229 grams (1 mole); Add back refluxing and stirring 24 hours, the tosic acid (1 gram) that cooling adds catalytic amount is back flow reaction 24 hours again, revolves dried; Re-crystallizing in ethyl acetate obtains 236 gram title products (yield 80%).
Claims (5)
1. described 3-sec.-propyl-(1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic, and raw material cyanic acid class includes but are not limited to acetonitrile, positive propionitrile, and different third is fine, uncle's butyronitrile, isopropyl cyanide, n-Butyronitrile, positive valeronitrile, isovaleronitrile, nitrile-hexyl or the like.
2. described 3-sec.-propyl-(1,2,4) oxadiazole-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic, and the raw material acids includes but are not limited to the 4-carbonyl tert-butyl ester-1 formic acid, acetate, propionic acid, cyclopropionate, butanic acid, ring butyric acid, chaulmoogric acid etc.
3. said 3-sec.-propyl-(1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic, is comprised by (2) and (3) one pot reaction solution but is not limited only to toluene, YLENE, benzene, dioxane, 1,2-ethylene dichloride etc.
4. said 3-sec.-propyl-(1,2,4) oxadiazoles-5-piperidines-1-carbonyl tert-butyl ester compounds is synthetic to be comprised by (2) and (3) one pot reaction temperature but is not limited only to 0 degree centigrade to 200 degrees centigrade.
5. said 3-sec.-propyl-(1,2,4) oxadiazole-5-piperidines-1-carbonyl tert-butyl ester compounds synthesizes one kettle way, purifying not midway, last Unified Treatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101533911A CN102702183A (en) | 2012-05-17 | 2012-05-17 | New synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101533911A CN102702183A (en) | 2012-05-17 | 2012-05-17 | New synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds |
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| Publication Number | Publication Date |
|---|---|
| CN102702183A true CN102702183A (en) | 2012-10-03 |
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| CN2012101533911A Pending CN102702183A (en) | 2012-05-17 | 2012-05-17 | New synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080188478A1 (en) * | 2005-04-26 | 2008-08-07 | Pfizer Inc. | Compounds Useful In Therapy |
| CN102070513A (en) * | 2011-01-20 | 2011-05-25 | 兰州博实生化科技有限责任公司 | Synthesis method of 1-teriary butoxy carbonyl-4-piperidone |
| TW201202230A (en) * | 2010-05-24 | 2012-01-16 | Mitsubishi Tanabe Pharma Corp | Novel quinazoline compound |
-
2012
- 2012-05-17 CN CN2012101533911A patent/CN102702183A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080188478A1 (en) * | 2005-04-26 | 2008-08-07 | Pfizer Inc. | Compounds Useful In Therapy |
| TW201202230A (en) * | 2010-05-24 | 2012-01-16 | Mitsubishi Tanabe Pharma Corp | Novel quinazoline compound |
| CN102070513A (en) * | 2011-01-20 | 2011-05-25 | 兰州博实生化科技有限责任公司 | Synthesis method of 1-teriary butoxy carbonyl-4-piperidone |
Non-Patent Citations (1)
| Title |
|---|
| GRAEME SEMPLE，等: "Discovery of the First Potent and Orally Efficacious Agonist of the Orphan G-Protein Coupled Receptor 119", 《J.MED.CHEM》 * |
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Application publication date: 20121003 |