CN103880765B - A kind of chemical synthesis process of 3 isoxazolyl acetic acid benzyl fat - Google Patents
A kind of chemical synthesis process of 3 isoxazolyl acetic acid benzyl fat Download PDFInfo
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- CN103880765B CN103880765B CN201410065193.9A CN201410065193A CN103880765B CN 103880765 B CN103880765 B CN 103880765B CN 201410065193 A CN201410065193 A CN 201410065193A CN 103880765 B CN103880765 B CN 103880765B
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- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 33
- QSMYAUJWSXKKDS-UHFFFAOYSA-N 2-(1,2-oxazol-3-yl)acetic acid Chemical compound OC(=O)CC=1C=CON=1 QSMYAUJWSXKKDS-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 39
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims abstract description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 16
- -1 isoxazolyl benzyl Chemical group 0.000 claims abstract description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 12
- MKFCBJOVMMLPRT-UHFFFAOYSA-N 3-(chloromethyl)-1,2-oxazole Chemical class ClCC=1C=CON=1 MKFCBJOVMMLPRT-UHFFFAOYSA-N 0.000 claims abstract description 10
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims abstract description 10
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 7
- 235000019445 benzyl alcohol Nutrition 0.000 claims abstract description 6
- 229960004217 benzyl alcohol Drugs 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- 230000007062 hydrolysis Effects 0.000 claims abstract description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
- VGYYSIDKAKXZEE-UHFFFAOYSA-L hydroxylammonium sulfate Chemical compound O[NH3+].O[NH3+].[O-]S([O-])(=O)=O VGYYSIDKAKXZEE-UHFFFAOYSA-L 0.000 claims abstract description 3
- 229910000378 hydroxylammonium sulfate Inorganic materials 0.000 claims abstract description 3
- 239000002994 raw material Substances 0.000 claims abstract description 3
- QUKGYYKBILRGFE-UHFFFAOYSA-N benzyloxyacetoaldehyde Natural products CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 claims abstract 11
- 229940007550 benzyl acetate Drugs 0.000 claims abstract 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- SEVIEHFDUHCSCV-UHFFFAOYSA-N 1-chlorobut-3-en-2-one Chemical class ClCC(=O)C=C SEVIEHFDUHCSCV-UHFFFAOYSA-N 0.000 claims description 13
- 238000010992 reflux Methods 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 18
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 230000032050 esterification Effects 0.000 abstract description 2
- 238000005886 esterification reaction Methods 0.000 abstract description 2
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 abstract 4
- 125000003963 dichloro group Chemical group Cl* 0.000 abstract 2
- 238000005406 washing Methods 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 238000001035 drying Methods 0.000 description 15
- 238000000605 extraction Methods 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000000376 reactant Substances 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 150000002545 isoxazoles Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Abstract
The present invention relates to a kind of chemical synthesis process of 3 isoxazolyl benzyl acetate.The present invention, by improving yield through addition, contracting ring, substitution, hydrolysis and esterification five steps reaction, a kind of method efficiently synthesized is provided for the synthesis of the compound using chloracetyl chloride and acetylene as raw material.The key step of the inventive method is as follows：Acetylene, chloracetyl chloride, catalyst alchlor and tetrahydrofuran solvent are added in reactor, after reaction terminates, separate to obtain the butenone of Isosorbide-5-Nitrae dichloro 3；The butenone of Isosorbide-5-Nitrae dichloro 3 and hydroxylammonium sulfate are added in methanol or alcohol solvent, controlling reaction temperature, reaction obtains 3 chloromethyl isoxazoles；Prepare 3 isoxazole acetonitriles；3 isoxazole acetonitriles are added in hydrochloric acid, hydrolysis obtains 3 isoxazole acetic acid；3 isoxazole acetic acid and benzylalcohol are added in dichloromethane or chloroform solvent, thionyl chloride is added and catalyst n, N dimethylformamides reacts to obtain 3 isoxazolyl benzyl acetates.
Description
Technical field
The present invention relates to a kind of chemical synthesis process of 3- isoxazolyls acetic acid benzyl fat.
Background technology
Isoxazole and its derivative are a kind of important five member ring heterocyclic compounds, they be not only organic synthesis it is important in
Mesosome, and the important feature unit of bioactive molecule and natural products.Isoxazole derivatives has extensive in medicine
Using its main pharmacological activity has analgesic, anti-inflammatory, anticonvulsion, antibacterial, excitor nerve etc.；Tong Shi isoxazole derivativeses are killing
Worm, sterilizing, weeding etc. also show good effect.Especially in recent decades, constantly there are new isoxazole derivativeses
Agricultural chemicals or Iatrochemistry product are developed to, so as to effectively promote the development of isoxazole chemistry.
3- isoxazolyls acetic acid benzyl fat after structure derivative, there is extensive pharmacology to live as a kind of isoxazole derivatives
Property, there is application in terms of antibacterial, antiviral, the various osteopathy for the treatment of or prevention, antidepressant activity and Antianxiety Activity, thus it is right
The study on the synthesis of the compound has important practical significance.
The content of the invention
It is an object of the invention to provide a kind of chemical synthesis route of 3- isoxazolyls acetic acid benzyl fat.
Technical scheme is as follows：
A kind of chemical synthesis process of 3- isoxazolyls acetic acid benzyl fat, it is characterised in that using chloracetyl chloride and acetylene as original
Material, reacted through five steps, synthesized 3- isoxazolyl benzyl acetates, synthetic route is as follows：
Described chemical synthesis process is:
（A）Acetylene, chloracetyl chloride, catalyst alchlor and tetrahydrofuran solvent are added in reactor, reaction knot
Shu Hou, separate to obtain the chloro- 3- butenones of Isosorbide-5-Nitrae-two；
（B）The chloro- 3- butenones of Isosorbide-5-Nitrae-two and hydroxylammonium sulfate are added in methanol or alcohol solvent, controlling reaction temperature, instead
3- chloromethyl isoxazoles should be obtained；
（C）3- chloromethyl isoxazoles and cuprous cyanide are added in organic solvent, described organic solvent is N, N- diformazans
One kind in base formamide, DMF, dimethyl sulfoxide (DMSO), reaction prepare 3- isoxazole acetonitriles；
（D）3- isoxazoles acetonitrile is added in hydrochloric acid, hydrolysis obtains 3- isoxazole acetic acid；
（E）3- isoxazoles acetic acid and benzylalcohol are added in dichloromethane or chloroform solvent, thionyl chloride is added and urges
Agent N,N-dimethylformamide reacts to obtain 3- isoxazolyl benzyl acetates.
Further, in step, the reaction temperature is 10-50 DEG C.
Further, in stepb, the reaction temperature is 20-80 DEG C.
Further, in step C, the reaction temperature is 10-50 DEG C.
Further, in step D, described concentration of hydrochloric acid is 1-12M, and reaction temperature is 60-100 DEG C.
Further, in step E, the reaction is carried out at reflux.
The beneficial effects of the present invention are：The chemical synthesis process of the present invention, using chloracetyl chloride and acetylene as raw material, through adding
Yield is improved into, contracting ring, substitution, hydrolysis and esterification five steps reaction, one kind is provided for the synthesis of the compound and efficiently synthesizes
Method.
Embodiment
In order to deepen the understanding to the present invention, below in conjunction with embodiment, the invention will be further described, following implementation
Example is only used for explaining the present invention, is not intended to limit the scope of the present invention..
Embodiment 1
The synthesis of the chloro- 3- butenones of 1,4- bis-：
Tetrahydrofuran 200mL, chloracetyl chloride 50.0g and alchlor 60.0g are added in there-necked flask, at 30 DEG C, is passed through
Acetylene solid/liquid/gas reactions 8h.Reactant is poured into 500mL frozen water, chloroform extraction（100mL×3）, merge organic phase.Washing,
Saturated sodium bicarbonate is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give the chloro- 3- butenones 58.6g of Isosorbide-5-Nitrae-two
（95.2%）.
The synthesis of 3- chloromethyl isoxazoles：
400mL ethanol, the chloro- 3- butenones of 50.0g1,4- bis- and 31.0g HASs are added in there-necked flask.It is heated to
Reacted under reflux state, thin-layer chromatography detection reaction is to terminal.Reactant is poured into 500mL frozen water, dichloromethane extraction
（100mL×3）, merge organic phase.Washing, saturated sodium bicarbonate are washed, saturated common salt washing, anhydrous sodium sulfate drying, decompression essence
Evaporate and collect 3- chloromethyl isoxazoles 33.1g（78.3%）.
The synthesis of 3- isoxazole acetonitriles：
200mL dimethyl sulfoxide (DMSO)s and 30.0g3- chloromethyl isoxazoles are added in there-necked flask, adds cuprous cyanide 21.5g.
30 DEG C, after reaction terminates are heated to, adds 500mL water, dichloromethane extraction（100mL×3）, merge organic phase.Washing, saturation
Sodium acid carbonate is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give 3- isoxazole acetonitriles 23.8g（86.3%）.
The synthesis of 3- isoxazole acetic acid：
20.0g3- isoxazoles acetonitrile and 100mL8M hydrochloric acid are added in there-necked flask, is heated to 80 DEG C of reactions.Reaction knot
Shu Hou, it is 7.0 or so that dilute sodium acid carbonate, which adjusts pH, dichloromethane extraction（70mL×3）, merge organic phase.Washing, saturated aqueous common salt
Wash, anhydrous sodium sulfate drying, be concentrated to give 3- isoxazole acetic acid 22.2g（94.4%）.
The synthesis of 3- isoxazolyl benzyl acetates：
150mL chloroforms, 3- isoxazole acetic acid 20.0g and benzylalcohol 22.0g are added in there-necked flask, is added after dissolving
Thionyl chloride 28.0g and N,N-dimethylformamide 0.5g.It is heated to reflux state reaction.After reaction terminates, wash three times.It is dilute
Sodium bicarbonate aqueous solution is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give 3- isoxazolyl benzyl acetates 32.0g
（93.6%）.
Embodiment 2
The synthesis of the chloro- 3- butenones of 1,4- bis-：
Toluene 200mL, chloracetyl chloride 50.0g and alchlor 60.0g are added in there-necked flask, at 40 DEG C, is passed through acetylene
Solid/liquid/gas reactions 8h.Reactant is poured into 500mL frozen water, chloroform extraction（100mL×3）, merge organic phase.Washing, saturation
Sodium acid carbonate is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give the chloro- 3- butenones 57.8g of Isosorbide-5-Nitrae-two（93.9%）.
The synthesis of 3- chloromethyl isoxazoles：
400mL methanol, the chloro- 3- butenones of 50.0g1,4- bis- and 31.0g HASs are added in there-necked flask.It is heated to
Reacted under reflux state, thin-layer chromatography detection reaction is to terminal.Reactant is poured into 500mL frozen water, dichloromethane extraction
（100mL×3）, merge organic phase.Washing, saturated sodium bicarbonate are washed, saturated common salt washing, anhydrous sodium sulfate drying, decompression essence
Evaporate and collect 3- chloromethyl isoxazoles 30.7g（72.6%）.
The synthesis of 3- isoxazole acetonitriles：
200mL DMFs and 30.0g3- chloromethyl isoxazoles are added in there-necked flask, it is sub- to add cyaniding
Copper 21.5g.30 DEG C, after reaction terminates are heated to, adds 500mL water, dichloromethane extraction（100mL×3）, merge organic phase.
Washing, saturated sodium bicarbonate are washed, and saturated common salt washing, anhydrous sodium sulfate drying, are concentrated to give 3- isoxazole acetonitriles 22.9g
（83.0%）.
The synthesis of 3- isoxazole acetic acid：
20.0g3- isoxazoles acetonitrile and 100mL6M hydrochloric acid are added in there-necked flask, is heated to 90 DEG C of reactions.Reaction knot
Shu Hou, it is 7.0 or so that dilute sodium acid carbonate, which adjusts pH, dichloromethane extraction（70mL×3）, merge organic phase.Washing, saturated aqueous common salt
Wash, anhydrous sodium sulfate drying, be concentrated to give 3- isoxazole acetic acid 21.5g（91.4%）.
The synthesis of 3- isoxazolyl benzyl acetates：
150mL dichloromethane, 3- isoxazole acetic acid 20.0g and benzylalcohol 22.0g are added in there-necked flask, is added after dissolving
Thionyl chloride 28.0g and N,N-dimethylformamide 0.5g.It is heated to reflux state reaction.After reaction terminates, wash three times.It is dilute
Sodium bicarbonate aqueous solution is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give 3- isoxazolyl benzyl acetates 31.1g
（91.0%）.
Embodiment 3
The synthesis of the chloro- 3- butenones of 1,4- bis-：
Tetrahydrofuran 200mL, chloracetyl chloride 50.0g and alchlor 60.0g are added in there-necked flask, at 50 DEG C, is passed through
Acetylene solid/liquid/gas reactions 8h.Reactant is poured into 500mL frozen water, chloroform extraction（100mL×3）, merge organic phase.Washing,
Saturated sodium bicarbonate is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give the chloro- 3- butenones 51.7g of Isosorbide-5-Nitrae-two
（84.0%）.
The synthesis of 3- chloromethyl isoxazoles：
400mL ethanol, the chloro- 3- butenones of 50.0g1,4- bis- and 31.0g HASs are added in there-necked flask.It is heated to
60 DEG C of reactions, thin-layer chromatography detection reaction is to terminal.Reactant is poured into 500mL frozen water, dichloromethane extraction（100mL×
3）, merge organic phase.Washing, saturated sodium bicarbonate are washed, saturated common salt washing, anhydrous sodium sulfate drying, and 3- is collected in rectification under vacuum
Chloromethyl isoxazole 31.2g（73.8%）.
The synthesis of 3- isoxazole acetonitriles：
200mL dimethyl sulfoxide (DMSO)s and 30.0g3- chloromethyl isoxazoles are added in there-necked flask, adds cuprous cyanide 21.5g.
40 DEG C, after reaction terminates are heated to, adds 500mL water, dichloromethane extraction（100mL×3）, merge organic phase.Washing, saturation
Sodium acid carbonate is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give 3- isoxazole acetonitriles 24.5g（88.8%）.
The synthesis of 3- isoxazole acetic acid：
20.0g3- isoxazoles acetonitrile and 100mL10M hydrochloric acid are added in there-necked flask, is heated to 80 DEG C of reactions.Reaction knot
Shu Hou, it is 7.0 or so that dilute sodium acid carbonate, which adjusts pH, dichloromethane extraction（70mL×3）, merge organic phase.Washing, saturated aqueous common salt
Wash, anhydrous sodium sulfate drying, be concentrated to give 3- isoxazole acetic acid 22.4g（95.3%）.
The synthesis of 3- isoxazolyl benzyl acetates：
150mL chloroforms, 3- isoxazole acetic acid 20.0g and benzylalcohol 22.0g are added in there-necked flask, is added after dissolving
Thionyl chloride 28.0g and N,N-dimethylformamide 1.0g.It is heated to reflux state reaction.After reaction terminates, wash three times.It is dilute
Sodium bicarbonate aqueous solution is washed, and saturated common salt washing, anhydrous sodium sulfate drying, is concentrated to give 3- isoxazolyl benzyl acetates 32.8g
（95.9%）.
Claims (5)
- A kind of 1. chemical synthesis process of 3- isoxazolyls benzyl acetate, it is characterised in that using chloracetyl chloride and acetylene as raw material, Reacted through five steps, synthesized 3- isoxazolyl benzyl acetates, synthetic route is as follows：Described chemical synthesis process is:(A) acetylene, chloracetyl chloride, catalyst alchlor and tetrahydrofuran solvent are added in reactor, after reaction terminates, Separate to obtain the chloro- 3- butenones of 1,4- bis-；(B) the chloro- 3- butenones of Isosorbide-5-Nitrae-two and hydroxylammonium sulfate are added in methanol or alcohol solvent, controlling reaction temperature, reacted To 3- chloromethyl isoxazoles；(C) 3- chloromethyl isoxazoles and cuprous cyanide are added in organic solvent, described organic solvent is N, N- dimethyl methyls One kind in acid amides, dimethyl sulfoxide (DMSO), reaction prepare 3- isoxazole acetonitriles；(D) 3- isoxazoles acetonitrile is added in hydrochloric acid, hydrolysis obtains 3- isoxazole acetic acid；(E) 3- isoxazoles acetic acid and benzylalcohol are added in dichloromethane or chloroform solvent, adds thionyl chloride and catalyst N,N-dimethylformamide reacts to obtain 3- isoxazolyl benzyl acetates；In step, the reaction temperature is 10-50 DEG C.
- A kind of 2. chemical synthesis process of 3- isoxazolyls benzyl acetate according to claim 1, it is characterised in that：In step In rapid B, the reaction temperature is 20-80 DEG C.
- A kind of 3. chemical synthesis process of 3- isoxazolyls benzyl acetate according to claim 1, it is characterised in that：In step In rapid C, the reaction temperature is 10-50 DEG C.
- A kind of 4. chemical synthesis process of 3- isoxazolyls benzyl acetate according to claim 1, it is characterised in that：In step In rapid D, described concentration of hydrochloric acid is 1-12M, and reaction temperature is 60-100 DEG C.
- A kind of 5. chemical synthesis process of 3- isoxazolyls benzyl acetate according to claim 1, it is characterised in that：In step In rapid E, the reaction is carried out at reflux.
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| CN103242256A (en) * | 2013-05-21 | 2013-08-14 | 苏州科捷生物医药有限公司 | Synthetic method of 3-aminomethyl-isoxazole hydrochloride |
| WO2014018807A1 (en) * | 2012-07-26 | 2014-01-30 | Centrax International, Inc. | Peptide epoxyketone compounds |
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|---|---|---|---|---|
| WO2014018807A1 (en) * | 2012-07-26 | 2014-01-30 | Centrax International, Inc. | Peptide epoxyketone compounds |
| CN103242256A (en) * | 2013-05-21 | 2013-08-14 | 苏州科捷生物医药有限公司 | Synthetic method of 3-aminomethyl-isoxazole hydrochloride |
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