CN101723920B - Process for synthesizing (R)-Glycidyl butyrate - Google Patents
Process for synthesizing (R)-Glycidyl butyrate Download PDFInfo
- Publication number
- CN101723920B CN101723920B CN200910153722XA CN200910153722A CN101723920B CN 101723920 B CN101723920 B CN 101723920B CN 200910153722X A CN200910153722X A CN 200910153722XA CN 200910153722 A CN200910153722 A CN 200910153722A CN 101723920 B CN101723920 B CN 101723920B
- Authority
- CN
- China
- Prior art keywords
- methylene dichloride
- organic layer
- hours
- acetone
- glycidyl butyrate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- YLNSNVGRSIOCEU-ZCFIWIBFSA-N [(2r)-oxiran-2-yl]methyl butanoate Chemical compound CCCC(=O)OC[C@H]1CO1 YLNSNVGRSIOCEU-ZCFIWIBFSA-N 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 63
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 36
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 18
- 238000001035 drying Methods 0.000 claims abstract description 18
- 239000012044 organic layer Substances 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 14
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 12
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- 150000001844 chromium Chemical class 0.000 claims abstract description 4
- -1 (S)-3-chloro-2-hydroxypropyl butyric ester Chemical compound 0.000 claims description 16
- 235000017550 sodium carbonate Nutrition 0.000 claims description 11
- LRWZZZWJMFNZIK-ZJRLKYRESA-N (2s)-2-chloro-3-methyloxirane Chemical compound CC1O[C@H]1Cl LRWZZZWJMFNZIK-ZJRLKYRESA-N 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 235000015320 potassium carbonate Nutrition 0.000 claims description 6
- 238000010025 steaming Methods 0.000 claims description 6
- 229910021555 Chromium Chloride Inorganic materials 0.000 claims description 5
- QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 claims description 5
- WYYQVWLEPYFFLP-UHFFFAOYSA-K chromium(3+);triacetate Chemical compound [Cr+3].CC([O-])=O.CC([O-])=O.CC([O-])=O WYYQVWLEPYFFLP-UHFFFAOYSA-K 0.000 claims description 3
- GRWVQDDAKZFPFI-UHFFFAOYSA-H chromium(III) sulfate Chemical compound [Cr+3].[Cr+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRWVQDDAKZFPFI-UHFFFAOYSA-H 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 238000005406 washing Methods 0.000 abstract description 13
- 239000002994 raw material Substances 0.000 abstract description 6
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 238000001704 evaporation Methods 0.000 abstract 3
- 238000001816 cooling Methods 0.000 abstract 2
- BRLQWZUYTZBJKN-GSVOUGTGSA-N (+)-Epichlorohydrin Chemical compound ClC[C@@H]1CO1 BRLQWZUYTZBJKN-GSVOUGTGSA-N 0.000 abstract 1
- PKWBKUUALJRCAQ-ZCFIWIBFSA-N [(2s)-3-chloro-2-hydroxypropyl] butanoate Chemical compound CCCC(=O)OC[C@H](O)CCl PKWBKUUALJRCAQ-ZCFIWIBFSA-N 0.000 abstract 1
- 239000012141 concentrate Substances 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 12
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 description 6
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 6
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000008034 disappearance Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- 230000007071 enzymatic hydrolysis Effects 0.000 description 2
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 2
- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 2
- 229960003907 linezolid Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- YLNSNVGRSIOCEU-UHFFFAOYSA-N oxiran-2-ylmethyl butanoate Chemical compound CCCC(=O)OCC1CO1 YLNSNVGRSIOCEU-UHFFFAOYSA-N 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- LRWZZZWJMFNZIK-NFJMKROFSA-N (2R)-2-chloro-3-methyloxirane Chemical compound CC1O[C@@H]1Cl LRWZZZWJMFNZIK-NFJMKROFSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- SWEYNHYBJHPVJL-UHFFFAOYSA-N butanoic acid;sodium Chemical compound [Na].CCCC(O)=O SWEYNHYBJHPVJL-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000000711 polarimetry Methods 0.000 description 1
- RWMKSKOZLCXHOK-UHFFFAOYSA-M potassium;butanoate Chemical compound [K+].CCCC([O-])=O RWMKSKOZLCXHOK-UHFFFAOYSA-M 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
Landscapes
- Epoxy Compounds (AREA)
Abstract
The invention discloses a process for synthesizing (R)-Glycidyl butyrate, which comprises the following steps: in the presence of a catalyst chromium salt, reacting (S)-epichlorohydrin with n-butyric acid in a molar ratio of 1:1-4 at the temperature of between 60 and 80 DEG C for 24 to 48 hours; cooling to the temperature of between 10 and 20 DEG C, adding methylene dichloride, neutralizing with 10 mass percent sodium carbonate solution until the pH is equal to 7.0-8.0, washing with water for 2 to 3 times, standing and demixing; drying an organic layer with anhydrous sodium sulfate, evaporating to remove the methylene dichloride, taking acetone as a solvent, performing reflux reaction on (S)-3-chloro-2-hydroxypropyl butyrate and carbonate of which the molar ratio is 1:1-3 for 10 to12 hours, cooling to the temperature of between 10 and 20 DEG C, filtering, removing undissolved substances, and evaporating to remove the acetone to obtain a concentrate; and adding 200 to 500mL of methylene dichloride, washing with water for 2 to 3 times, drying an organic layer with anhydrous sodium sulfate, evaporating to remove the methylene dichloride, rectifying to collect fractions with the temperature of between 55 and 65 DEG C in the vacuum degree of between 60 and 70Pa, and obtaining the product (R)-Glycidyl butyrate. The process has the advantages of simple raw materials, mild reaction conditions, environmental protection, and suitability for industrial production.
Description
Technical field
The present invention relates to the synthesis technique of compound, relate in particular to a kind of synthesis technique of (R)-Glycidyl butyrate.
Background technology
Morpholine uh ketone (Linezolid U-100766) be in April, 2000 at the complete synthesis antibiotic new drug of U.S.'s approval listing, be used for the treatment of skin and skin histology infection, pneumonia and faecalis and infect.In this chiral drug molecule 5 chiral carbon atoms of morpholine ring to be configured as the S type effective.In its building-up process, need an important intermediate: (R)-the Racemic glycidol butyric ester.(R)-the Racemic glycidol butyric ester generally can pass through enzymatic hydrolysis; Methods such as asymmetric synthesis prepare.
Enzymatic hydrolysis: first synthesising racemation body Racemic glycidol butyric ester, split through biology again, obtain enantiomorph (M atson S L.WO, 88 07,582 (1988) of single configuration; Amano M, Toda H, Tanaka S.JP, 63 173 597 (1988); Whitesides G M, L ader W.U S, 4,732,853 (1988)).Wherein raceme compound Racemic glycidol butyric ester is synthetic, obtains by epoxy chloropropane and Potassium n-butyrate generation nucleophilic substitution reaction.(R)-under the effect of enzyme, the generation enzymically hydrolyse reacts and splits the Racemic glycidol butyric ester by raceme Racemic glycidol butyric ester.Catalytic biological method for splitting, the reaction conditions gentleness, by product is few, and product separation is purified simple, and production safety is effective.The reaction that enzyme is participated in has the stereospecificity of height usually, and the polarimetry purity that therefore obtains product is higher, and enzyme easily degrades, and can not cause environmental pollution, is suitable for scale operation.But because the kind of enzyme is limited, and enzyme is destroyed easily, and reaction can only obtain a kind of enantiomorph wherein, and the maximum yield of reaction also has only 50%, so this method has certain limitation.
Asymmetric synthesis: by naturally occurring chipal compounds D-N.F,USP MANNITOL is starting raw material (Baldwin JJ, Raab A W.J.Org.Chem., 1978,43 (25): 4876; Jung M E, Shaw T J.J.Am.Chem.Soc., 1980,102 (20): 6304), it is carried out effective chemical modify and transform.With N.F,USP MANNITOL is that raw material reacts, and reactant and intermediate are easy to epimerization under acid-base condition, and transport reaction takes place product easily, causes racemization and can not get desired (R)-Glycidyl butyrate.
Horse wait quietly (Ma Jing, Xue Feiqun. chemical reagent, 2002,24 (1) 19-21) be that starting raw material and butanic acid sodium react direct synthetic butyric acid glycidyl ester with (R)-epoxy chloropropane, but the product racemization can not get desired (R)-Glycidyl butyrate.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of synthesis technique of (R)-Glycidyl butyrate is provided.
(R)-synthesis technique of Glycidyl butyrate comprises the steps:
1) under the catalyst chromium salt action, mol ratio is that (S)-epoxy chloropropane of 1: 1～4 and butanic acid were 60～80 ℃ of reactions 24～48 hours, be cooled to 10～20 ℃, add methylene dichloride, be neutralized to pH=7.0～8.0, wash with water again 2～3 times with mass percent 10% sodium carbonate solution, standing demix, the organic layer anhydrous sodium sulfate drying, steaming vibrating dichloromethane gets (S)-3-chloro-2-hydroxypropyl butyric ester;
2) with acetone be solvent, mol ratio is (S)-3-chloro-2-hydroxypropyl butyric ester of 1: 1～3 and carbonate back flow reaction 10～12 hours, is cooled to 10～20 ℃, filter, remove insolubles, boil off acetone, obtain enriched material, add 200～500mL methylene dichloride, wash the organic layer anhydrous sodium sulfate drying with water 2～3 times, steaming vibrating dichloromethane, 55～65 ℃ of fractions are collected in rectifying, and vacuum tightness 60～70Pa gets product (R)-Glycidyl butyrate.
The mol ratio of described (S)-epoxy chloropropane and butanic acid is preferably 1: 1～and 2.Described catalyzer chromic salts is chromium chloride, chromium acetate or chromium sulphate.Described carbonate is salt of wormwood or yellow soda ash.
Raw material of the present invention is simple, the reaction conditions gentleness, and environmental friendliness, the optical purity height of product can be used for industrialized production.
Embodiment
Reaction equation of the present invention is as follows:
Under the catalyst chromium salt action, butanic acid with (S)-epoxy chloropropane 60～80 ℃ the reaction 24～48 hours, be cooled to 10～20 ℃, add methylene dichloride, be neutralized to pH=8.0, wash with water again 3 times with 10% sodium carbonate solution, standing demix, the organic layer anhydrous sodium sulfate drying boils off solvent, gets (S)-3-chloro-2-hydroxypropyl butyric ester.
With acetone is solvent, (S)-and 3-chloro-2-hydroxypropyl butyric ester and carbonate back flow reaction 10～12 hours.Be cooled to 10～20 ℃, filter, remove insolubles, boil off acetone, obtain enriched material, add the 250mL methylene dichloride, water 50mL * 2 washings, organic layer anhydrous sodium sulfate drying, boil off solvent, 55-65 ℃ of fraction collected in rectifying, and vacuum tightness 60-70Pa gets product (R)-Glycidyl butyrate.
This method raw material is simple, and reaction conditions is not harsh, and cost is low, can be used for industrialized production.
Embodiment 1
250mL four in drop into 1mol butanic acid, 1mol (S)-epoxy chloropropane, chromium chloride 1g in the flask, stirring is warmed up to 60 ℃, be incubated 48 hours to the epoxy chloropropane disappearance, be cooled to 10 ℃, 250mL adds methylene chloride, be neutralized to pH=8.0 with 10% sodium carbonate solution, use the 300mL water washing again 3 times, the organic layer anhydrous sodium sulfate drying boils off solvent, get (S)-3-chloro-2-hydroxypropyl butyric ester 153g
1H NMR0.96 (3H, t), 1.72 (2H, m), 2.25 (2H, t), 4.20 (2H, d), 4.13 (H, m), 3.55 (2H, d), 1.8 (H), yield: 85.0%.
In the 1000mL four-hole boiling flask, add above-mentioned all (S)-3-chloro-2-hydroxypropyl butyric esters, acetone 600mL, salt of wormwood 2mol, back flow reaction 10 hours is to terminal.The elimination insolubles boils off acetone, gets enriched material and adds the 250mL methylene dichloride, water 100mL washing 2 times, the organic layer anhydrous sodium sulfate drying boils off solvent, and 55-65 ℃ of fraction, vacuum tightness 60-70Pa are collected in rectifying, get product (R)-Glycidyl butyrate 98.6g, specific rotation: 29.5 °
1H NMR 0.96 (3H, t), 1.70 (2H, m), 2.23 (2H, t), 2.63 (2H, d), 3.10 (1H, m), 4.31 (2H, d).Yield: 80.6%.
Embodiment 2
250mL four in drop into 2mol butanic acid, 1mol (S)-epoxy chloropropane, chromium acetate 1g in the flask, stirring is warmed up to 80 ℃, be incubated 24 hours to the epoxy chloropropane disappearance, be cooled to 20 ℃, 250mL adds methylene chloride, be neutralized to pH=8.0 with 10% sodium carbonate solution, use the 300mL water washing again 3 times, the organic layer anhydrous sodium sulfate drying boils off solvent, get (S)-3-chloro-2-hydroxypropyl butyric ester 126.9g, yield: 70.5%.
In the 1000mL four-hole boiling flask, add above-mentioned all (S)-3-chloro-2-hydroxypropyl butyric esters, acetone 600mL, yellow soda ash 2mol, back flow reaction 10 hours is to terminal.The elimination insolubles, boil off acetone, get enriched material and add the 250mL methylene dichloride, water 100mL washing 2 times, organic layer anhydrous sodium sulfate drying, boil off solvent, 55-65 ℃ of fraction collected in rectifying, and vacuum tightness 60-70Pa gets product (R)-Glycidyl butyrate 68.1g, specific rotation: 29.5 °, yield: 67.1%.
Embodiment 3
250mL four in drop into 1mol butanic acid, 1mol (S)-epoxy chloropropane, chromium sulphate 1g in the flask, stirring is warmed up to 80 ℃, be incubated 48 hours to the epoxy chloropropane disappearance, be cooled to 20 ℃, 250mL adds methylene chloride, be neutralized to pH=8.0 with 10% sodium carbonate solution, use the 300mL water washing again 3 times, the organic layer anhydrous sodium sulfate drying boils off solvent, get (S)-3-chloro-2-hydroxypropyl butyric ester 150.1g, yield: 83.4%.
In the 1000mL four-hole boiling flask, add above-mentioned all (S)-3-chloro-2-hydroxypropyl butyric esters, acetone 600mL, salt of wormwood 2mol, back flow reaction 12 hours is to terminal.The elimination insolubles, boil off acetone, get enriched material and add the 250mL methylene dichloride, water 100mL washing 2 times, organic layer anhydrous sodium sulfate drying, boil off solvent, 55-65 ℃ of fraction collected in rectifying, and vacuum tightness 60-70Pa gets product (R)-Glycidyl butyrate 105.4g, specific rotation: 28.9 °, yield: 87.8%.
Embodiment 4
250mL four in drop into 1mol butanic acid, 1mol (S)-epoxy chloropropane, chromium chloride 1g in the flask, stirring is warmed up to 60 ℃, be incubated 24 hours to the epoxy chloropropane disappearance, be cooled to 10 ℃, 250mL adds methylene chloride, be neutralized to pH=7.0 with 10% sodium carbonate solution, use the 200mL water washing again 2 times, the organic layer anhydrous sodium sulfate drying boils off solvent, get (S)-3-chloro-2-hydroxypropyl butyric ester 158.0g, yield: 87.8%.
In the 1000mL four-hole boiling flask, add 1mol (S)-3-chloro-2-hydroxypropyl butyric ester, acetone 600mL, salt of wormwood 2mol, back flow reaction was cooled to 10 ℃ in 10 hours to terminal, filtered, remove insolubles, boil off acetone, obtain enriched material, add the 200mL methylene dichloride, water 100mL washing 2 times, the organic layer anhydrous sodium sulfate drying, steaming vibrating dichloromethane, 55-65 ℃ of fraction collected in rectifying, vacuum tightness 60-70Pa, get product (R)-Glycidyl butyrate 123.3g, specific rotation: 29.5 °, yield: 85.6%.
Embodiment 5
500mL four in drop into 4mol butanic acid, 1mol (S)-epoxy chloropropane, chromium chloride 1g in the flask, stirring is warmed up to 80 ℃, be incubated 48 hours to the epoxy chloropropane disappearance, be cooled to 20 ℃, 250mL adds methylene chloride, be neutralized to pH=8.0 with 10% sodium carbonate solution, use the 300mL water washing again 3 times, the organic layer anhydrous sodium sulfate drying boils off solvent, get (S)-3-chloro-2-hydroxypropyl butyric ester 142.0g, yield: 78.9%.
In the 1000mL four-hole boiling flask, add 1mol (S)-3-chloro-2-hydroxypropyl butyric ester, acetone 600mL, salt of wormwood 3mol, back flow reaction was cooled to 20 ℃ in 12 hours to terminal, filtered, remove insolubles, boil off acetone, obtain enriched material, add the 500mL methylene dichloride, water 150mL washing 3 times, the organic layer anhydrous sodium sulfate drying, steaming vibrating dichloromethane, 55-65 ℃ of fraction collected in rectifying, vacuum tightness 60-70Pa, get product (R)-Glycidyl butyrate 117.5g, specific rotation: 29.5 °, yield: 81.6%.
Claims (2)
1. the synthesis technique of (R)-Glycidyl butyrate is characterized in that comprising the steps:
1) under the catalyst chromium salt action, mol ratio is that (S)-epoxy chloropropane of 1: 1～4 and butanic acid were 60～80 ℃ of reactions 24～48 hours, be cooled to 10～20 ℃, add methylene dichloride, be neutralized to pH=7.0～8.0, wash with water again 2～3 times with mass percent 10% sodium carbonate solution, standing demix, the organic layer anhydrous sodium sulfate drying, steaming vibrating dichloromethane gets (S)-3-chloro-2-hydroxypropyl butyric ester;
2) with acetone be solvent, mol ratio is (S)-3-chloro-2-hydroxypropyl butyric ester of 1: 1～3 and carbonate back flow reaction 10～12 hours, is cooled to 10～20 ℃, filter, remove insolubles, boil off acetone, obtain enriched material, add 200～500mL methylene dichloride, wash the organic layer anhydrous sodium sulfate drying with water 2～3 times, steaming vibrating dichloromethane, 55～65 ℃ of fractions are collected in rectifying, and vacuum tightness 60～70Pa gets product (R)-Glycidyl butyrate;
Described catalyzer chromic salts is chromium chloride, chromium acetate or chromium sulphate, and described carbonate is salt of wormwood or yellow soda ash.
2. the synthesis technique of a kind of (R)-Glycidyl butyrate according to claim 1, the mol ratio that it is characterized in that described (S)-epoxy chloropropane and butanic acid is 1: 1～2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910153722XA CN101723920B (en) | 2009-11-02 | 2009-11-02 | Process for synthesizing (R)-Glycidyl butyrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910153722XA CN101723920B (en) | 2009-11-02 | 2009-11-02 | Process for synthesizing (R)-Glycidyl butyrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101723920A CN101723920A (en) | 2010-06-09 |
| CN101723920B true CN101723920B (en) | 2011-08-24 |
Family
ID=42445545
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910153722XA Active CN101723920B (en) | 2009-11-02 | 2009-11-02 | Process for synthesizing (R)-Glycidyl butyrate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101723920B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101935182B1 (en) * | 2014-09-22 | 2019-01-03 | 미쯔비시 케미컬 주식회사 | Method for producing 3-chloro-2-hydroxypropyl (meth)acrylate and method for producing glycidyl (meth)acrylate |
-
2009
- 2009-11-02 CN CN200910153722XA patent/CN101723920B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN101723920A (en) | 2010-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1956953A (en) | Process for the preparation of optically pure 4-hydroxy-2-oxo-1-pyrrolidine acetamide | |
| CN102605034B (en) | Biological enzyme resolution method for preparing optically pure (S)-5-(4-fluorophenyl)-5-hydroxypentanoate | |
| CN104086439A (en) | Method for recovering pregabalin intermediate resolving agent (R)-(+)-alpha-phenylethylamine | |
| CN111072718A (en) | Preparation method of L-glufosinate-ammonium | |
| CN101723920B (en) | Process for synthesizing (R)-Glycidyl butyrate | |
| CN114214375B (en) | Preparation method of (R)-3-(4-halo-1H-pyrazol-1-yl)-3-cyclopentylpropionate | |
| US8912345B2 (en) | Method for preparing optically pure (−)-clausenamide compound | |
| CN102827902B (en) | Method for preparing 2'-deoxyuridine by chemical-biological enzyme method in combination | |
| CN103214421B (en) | The industrialized preparing process of 2-sulfydryl-1-Methylimidazole | |
| CN113699209A (en) | 7-ADCA recovery method | |
| CN109161577B (en) | Levo Corey lactone diol intermediate, preparation method and pharmaceutical application thereof | |
| CN102838437A (en) | Production method of amino-acid ester | |
| CN103319366B (en) | Lacosamide synthesis technology | |
| CN105461606B (en) | The preparation method of high-purity Lei Dipawei intermediates | |
| CN105368886A (en) | Process of using resin-immobilized halohydrin dehalogenase to catalytically synthesize (R)-4-cyan-3-hydroxy ethyl butyrate | |
| CN106480009B (en) | Immobilized amino acid ester acyl transferase and application thereof in preparation of glutamine dipeptide | |
| CN112195203B (en) | Method for synthesizing (S) -2-aminobutanamide by enzyme method | |
| CN111100026A (en) | Preparation method of taxol oxazole ring side chain intermediate | |
| CN101284797B (en) | Decomposing method of N-protected allyl glycinate | |
| CN102586346A (en) | Bio-catalytic method for preparing o-hydroxyphenylacetic acid | |
| CN101906052B (en) | Method for preparing D-m-hydroxyphenylglycine | |
| CN101012181A (en) | Resolution method of DL-p-chlorophenylalanine | |
| CN106520857B (en) | Method for synthesizing aztreonam by enzyme method | |
| CN105218371A (en) | The preparation method of optically pure 3-hydroxyl-4-(2,4,5-trifluorophenyl) ethyl butyrate | |
| CN106957239A (en) | A kind of preparation method of improved scheme for lacosamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |