CN101914023A - Preparation method of optically pure 4-aryl-2-hydroxy-butyric ester - Google Patents
Preparation method of optically pure 4-aryl-2-hydroxy-butyric ester Download PDFInfo
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Abstract
The invention relates to a preparation method of optically pure 4-aryl-2-hydroxy-butyric ester, which comprises the following steps of: carrying out catalytic hydrogenation on 4-aryl -2-oxo-butyric acid in an organic ether or alcohol solvent in the presence of the ruthenium complex of a biaryl axially chiral phosphine ligand and an acid additive to prepare optically pure 4-aryl-2-hydroxy-butyric acid; and then carrying out esterification to obtain the optically pure 4-aryl-2-hydroxy-butyric ester. Starting from the 4-aryl -2-oxo-butyric acid, in the presence of the ruthenium complex of the biaryl axially chiral phosphine ligand, which is used as a catalyst, and the acid additive, the preparation method uses asymmetrical catalytic hydrogenation and esterification to prepare the (R)-4-aryl-2-hydroxy-butyric ester. The invention has the advantages of high enantioselectivity and good repeatability and can improve ee value to be higher than 99% by using a simple recrystalization method. The reaction formula is disclosed in the specification of the invention.
Description
Technical field
That the present invention relates to is a kind of preparation method's of chemical material technical field, particularly a kind of optically pure 4-aryl-2-hydroxy-butyric ester preparation method.
Background technology
Optically pure 4-phenyl-2-hydroxyl-ethyl butyrate is that a kind of important medicine intermediate is widely used in medicine and field of new at present.Wherein (R)-4-phenyl-2-hydroxyl-ethyl butyrate is the important intermediate of preparation antihypertensive drug-Puli's class medicine.Puli's class medicine is the inhibitor of angiotensin-converting enzyme (ACE), is the very large antihypertensive drug of the present consumption of a class, accounts for 1/5th of whole hypertension drug market.
Find by prior art documents, at present a lot (Asymmetric Catalysis on Industrial Scale:Challenges, Approaches and Solutions of the method for preparation (R)-4-phenyl-2-hydroxyl-ethyl butyrate; Wiley-VCH:Weinheim, 2004.), relatively have the method for actual value to have following three kinds:
1) reduces corresponding ketone, split the ester or the carboxylic acid of racemization then.For 4-phenyl-2-hydroxyl-butyric acid, can adopt enzymatic kinetic resolution; With the Chiral Amine salify, recrystallization (J.Chem.Soc.Perkin Trans.I 1986,1011 then; EP329156,1989.).
2) ketone (Adv.Synth.Catal.2001,343,264 of use chemistry, microorganism or the latent chirality of enzymatic enantioselectivity reduction; Tetrahedron 2000,56, and 6497; Tetrahedron:Asymmetry 1998,9, and 2725; Adv.Synth.Catal.2008,350,426.).
3) use natural chiral source such as oxysuccinic acid to prepare (Tetrahedron:Asymmetry 2001,12,1583.).
In aforesaid method, the method reactions steps of fractionation is long, and half raw material can't utilize at least; Though the method efficiency ratio of asymmetric reduction is higher, reaction pair raw material 4-phenyl-2-oxo-ethyl butyrate purity requirement is very high.Impurity pure, not only reduce the speed of response and the turn over number of asymmetric hydrogenation greatly, and have influence on the optical purity of product.Because 4-phenyl-2-oxo-ethyl butyrate is high boiling liquid and less stable, upward difficult in the industrial production purification ratio, and expense is higher.
Utilize 4-phenyl-2-carbonyl-3-butenoic acid ethyl to carry out asymmetric hydrogenation in the prior art for raw material, with respect to 4-phenyl-2-carbonyl-ethyl butyrate, butenoic acid ethyl is convenient purifies, more stable, this method has solved the problem of ethyl butyrate instability and purity, the simple synthetic method of the initial feed 4-phenyl-2-carbonyl-3-butenoic acid of butenoic acid ethyl is with low cost simultaneously.But this asymmetric reaction needs at first with initial feed 4-phenyl-2-carbonyl-3-butenoic acid esterification, utilize chiral ruthenium catalyst to carry out the ethyl butyrate (ee:94%) that asymmetric hydrogenation obtains chirality then, in order further to improve the ee value of product, the chiral product ethyl butyrate is hydrolyzed into butyric acid, by recrystallization the ee value is brought up to more than 99%, esterification becomes optically pure ethyl butyrate once more, the entire operation process becomes loaded down with trivial details, cost increases and total recovery reduces (J.Org.Chem.2008,73,7209).
Summary of the invention
The present invention is directed to the prior art above shortcomings, the invention provides a kind of preparation method of optically pure 4-aryl-2-hydroxy-butyric ester.The present invention reacts the enantioselectivity height, and good reproducibility is increased to the ee value greater than 99% by easy recrystallization method.
The present invention is from 4-aryl-2-ketobutyric acid, and the ruthenium complex that uses biaryl standard shaft chiral phosphine ligand is as catalyzer and add acid additives, the method for (R)-4-aryl-2-butyric ester.
The present invention is achieved by the following technical solutions:
Method of the present invention is as follows:
In organic ethers or alcoholic solvent, 4-aryl-2-ketobutyric acid is in the presence of the ruthenium complex of biaryl standard shaft chiral phosphine ligand and acid additives common, through asymmetric catalytic hydrogenation reaction and esterification, prepare optically pure 4-aryl-2-hydroxybutyric acid, obtain optically pure 4-aryl-2-butyric ester through over-churning;
Described solvent is a kind of of tetrahydrofuran (THF), methyltetrahydrofuran, dioxane, dioxolane, glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol bisthioglycolate propyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diisopropyl ether and di-n-butyl ether organic ether kind solvent; Perhaps be a kind of of methyl alcohol, ethanol, Virahol and trimethyl carbinol organic liquid alcoholic solvent; It perhaps is the mixed solvent of above-mentioned ether and alcohol.
Described aryl is phenyl, naphthyl, substituted-phenyl or substituted naphthyl.
The substituted radical of described substituted-phenyl or substituted naphthyl is alkyl, alkoxyl group, halogen, amino or sulfydryl etc.
Described additive is organic sulfonic acids such as Hydrogen bromide, hydroiodic acid HI, hydrochloric acid, sulfuric acid, phosphoric acid, fluoroboric acid, boric acid, trifluoracetic acid or tosic acid; Preferred described additive is a Hydrogen bromide.
Described phosphine ligand L is biaryl standard shaft chiral phosphine ligands such as SunPhos, SegPhos, BINAP, DifluroPhos, and its molecular structural formula is as follows:
SunPhos SegPhos BINAP DifluroPhos。
Preferred described phosphine ligand L is SunPhos.
Described catalyzer is: RuLCl
2, [RuCl (benzene) (L)] Cl, [RuBr (benzene) (L)] Br, [RuCl (cymene) (L)] Cl, RuLCl
2(DMF)
m, [NH
2Me
2]
+[(RuClL)
2(μ-Cl
3)]; Preferred described catalyzer is that the complex compound of ruthenium and phosphine part is [RuCl (benzene) (R)-SunPhos] Cl.
Described asymmetric catalytic hydrogenation reaction and esterification, reaction formula is as follows:
Carry out during temperature that described being reflected at-20 is ℃-120 ℃; Preferred described temperature of reaction is 70-90 ℃.
Described reaction mol ratio is that 4-aryl-2-ketobutyric acid/catalyzer is 100/1 to 50000/1; Preferred described reaction mol ratio is that 4-aryl-2-ketobutyric acid/catalyzer is 10000/1.
Described ester group is C
1-C
6Straight chained alkyl or the alkyl or the substituted alkyl of side chain are arranged.
It is reaction substrate that the present invention adopts commercial 4-aryl-2-ketobutyric acid, with respect to 4-phenyl-2-oxo-ethyl butyrate or 4-phenyl-2-oxo-3-butenoic acid ethyl, this class substrate is industrial mass production, with low cost and be solid (under the normal temperature), physicochemical property is stable, purify easily, reaction enantioselectivity height, good reproducibility; The more important thing is direct chiral product (the R)-4-aryl-2-hydroxybutyric acid that obtains, can the ee value be increased to greater than 99% by easy recrystallization method.The present invention is a kind of method that can be used for industrial sector production practicality.
Description of drawings
Fig. 1 (R)-4-phenyl-2-hydroxyl-ethyl butyrate is a preparation antihypertensive drug intermediates reaction formula.
Embodiment
Below in conjunction with accompanying drawing embodiments of the invention are elaborated: present embodiment is being to implement under the prerequisite with the technical solution of the present invention, provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
Embodiment 1
Asymmetric catalyst [RuCl (benzene) (R)-SunPhos] Cl's is synthetic
In a 250mL Schlenk pipe, add [Ru (benzene) Cl
2]
2(100mg, 0.2mmol) and part (R)-SunPhos (300mg, 0.44mmol), system is by vacuum line, with nitrogen replacement three times, adds the new degassing EtOH/CH that steams
2Cl
2(30mL/30mL), with under the cooling of dry ice/acetone batch, outgas three times then, return to room temperature, heat 50 ℃ and reacted 1 hour. drain solvent, after vacuum is taken out 2 hours, the complex compound that obtains [RuCl (benzene) (R)-SunPhos] Cl,
31PNMR (121MHz, CDCl
3): 33.4 (d, J=63.8Hz), 40.5 (d, J=63.8Hz).
Embodiment 2
Asymmetric catalyst [RuBr (benzene) (R)-SunPhos] Br's is synthetic
In a 250mL Schlenk pipe, add [Ru (benzene) Br
2]
2(136mg, 0.2mmol) and part (R)-SunPhos (300mg, 0.44mmol), system is by vacuum line, with nitrogen replacement three times, adds the new degassing EtOH/CH that steams
2Cl
2(20mL/20mL), with under the cooling of dry ice/acetone batch, outgas three times then, return to room temperature, heat 50 ℃ and reacted 1 hour. drain solvent, after vacuum is taken out 2 hours, the complex compound that obtains [RuBr (benzene) (R)-SunPhos] Br.
31PNMR(121MHz，CDCl
3)：33.8(d，J＝64.0Hz)，40.8(d，J＝64.0Hz)。
Embodiment 3
Asymmetric catalyst [RuCl (Cymene) (R)-SunPhos] Cl's is synthetic
In a 250mL Schlenk pipe, add [Ru (Cymene) Cl
2]
2(130mg, 0.2mmol) and part (R)-SunPhos (300mg, 0.44mmol), system is by vacuum line, with nitrogen replacement three times, adds the new degassing EtOH/CH that steams
2Cl
2(30mL/30mL), with under the cooling of dry ice/acetone batch, outgas three times then, return to room temperature, heat 50 ℃ and reacted 1 hour, drain solvent, after vacuum is taken out 2 hours, the complex compound that obtains [RuCl (Cymene) (R)-SunPhos] Cl.
31PNMR(162MHz，CDCl
3)：28.4(d，J＝64.2Hz)，42.8(d，J＝63.8Hz)。
Embodiment 4
In a 250mL Schlenk pipe, add [Ru (benzene) Cl
2]
2(100mg, 0.2mmol) and part (R)-SunPhos (300mg, 0.44mmol), system is by vacuum line, with nitrogen replacement three times, adds the new degassing EtOH/CH that steams
2Cl
2(20mL/20mL), with under the cooling of dry ice/acetone batch, outgas three times then, return to room temperature, heated 50 ℃ hours. drain solvent, after vacuum is taken out 2 hours, the complex compound that obtains [RuCl (benzene) (R)-SunPhos] Cl, add dimethylamine hydrochloride (33mg, 0.4mmol), system is used nitrogen replacement three times by vacuum line, adds the new degassing dioxane (15mL) that steams, outgas three times, reflux 16 hours cools to 40 ℃, vacuum is drained solvent, obtains complex compound [NH
2Me
2]
+[RuCl[(R)-SunPhos]
2(μ-Cl
3)].
31P?NMR(162MHz，CDCl
3)：53.0(d，J＝41.0Hz)，54.5(d，J＝41.0Hz).
Embodiment 5
Asymmetric catalytic hydrogenation preparation (the R)-4-aryl-2-hydroxyl-butyric acid (ethyl ester) of 4-aryl-2-ketobutyric acid
In being placed with the autoclave of magnetic stir bar, add 4-phenyl-2-ketobutyric acid (3.56g, 20mmol), tetrahydrofuran (THF) (100mL) adds catalyzer [RuCl (benzene) (R)-SunPhos] Cl (19.1mg, 0.01mmol) and additive 1N HBr (0.12mL), sealing; Inject high-purity H
2(purity＞99.999%) is released to gas then carefully to 10atm, and triplicate adds hydrogen pressure for setting 30atm, and autoclave is airtight; Put into the oil bath that is heated to 90 ℃ in advance, magnetic agitation 20 hours, gas is carefully emitted in cooling, opens autoclave, takes out bottle, drains solvent, gets the data ee:93.9% of (R)-4-phenyl-2-hydroxybutyric acid crude acid.
1H?NMR(400MHz，CDCl
3)：1.97-2.05(m，1H)，2.14-2.23(m，1H)，2.80(t，J＝8.0Hz，2H)，4.27(dd，J＝4.0，8.0Hz，1H)，7.18-7.31(m，5H).
13C?NMR(100MHz，CDCl
3)：31.2，35.9，69.7，126.4，128.7，128.8，140.9，178.0.M.p.118-119℃.
Embodiment 6
(R)-4-phenyl-2-hydroxybutyric acid refining
With asymmetric hydrogenation product crude product (R)-4-phenyl-2-hydroxybutyric acid (3.3g, 18mmol) be dissolved in the 50mL ether, wash (3x10mL) with water, saturated aqueous common salt 10mL washes once, the organic phase diethyl ether solution restrains anhydrous sodium sulfate dryings with 2, remove the organic phase ether, product is dissolved in 10mL 1, recrystallization in the 2-ethylene dichloride, (3.0g 16mmol), obtains (R)-4-phenyl-2-3-hydroxyethyl butyrate behind over-churning to obtain white needle-like crystals (R)-4-phenyl-2-hydroxyl-butyric acid, yield 90%, the ee value is greater than 99%.Nuclear magnetic data:
1H NMR (400MHz, CDCl
3): 1.28 (t, J=7.2Hz, 3H), 1.90-1.99 (m, 1H), 2.10-2.16 (m, 1H), 2.70-2.79 (m, 2H), 2.81 (br, 1H), 4.17-4.20 (m, 1H), 4.21 (q, J=7.2Hz, 2H), 7.20-7.31 (m, 5H).
13C NMR (100MHz, CDCl
3): 14.0,30.9,35.8,61.5,69.6,125.8,128.2,128.4,141.0,175.1.
Embodiment 7
Asymmetric catalytic hydrogenation preparation (R)-4-(the 4-methyl)-phenyl-2-3-hydroxyethyl butyrate of 4-(4-methyl)-phenyl-2-ketobutyric acid
Operation is as described in the embodiment 5,6, uses [RuCl (benzene) (R)-SunPhos] Cl as catalyzer, (R)-4-(4-methyl)-phenyl-2-3-hydroxyethyl butyrate data: crude product ee:93.5%; Refining back yield: 90%; Ee:99.0%.Nuclear magnetic data:
1HNMR (400MHz, CDCl
3): 1.29 (t, J=7.2Hz, 3H), 1.87-1.97 (m, 1H), 2.05-2.14 (m, 1H), 2.32 (s, 3H), 2.66-2.78 (m, 2H), 2.84 (d, J=5.2Hz, 1H), 4.15-4.19 (m, 1H), 4.22 (q, J=7.2Hz, 2H), 7.10 (s, 4H).
13C NMR (100MHz, CDCl
3): 14.3,21.1,30.7,36.2,61.8,69.8,128.5,129.2,135.6,138.2,175.4.
Embodiment 8
Asymmetric catalytic hydrogenation preparation (R)-4-(the 4-methoxyl group)-phenyl-2-3-hydroxyethyl butyrate of 4-(4-methoxyl group)-phenyl-2-ketobutyric acid
Operation is as described in the embodiment 5,6, uses [RuCl (benzene) (R)-SunPhos] Cl as catalyzer, (R)-4-(4-methoxyl group)-phenyl-2-3-hydroxyethyl butyrate data: crude product ee:93.6%; Refining back yield: 90%; Ee:99.0%.Nuclear magnetic data:
1H NMR (400MHz, CDCl
3): 1.29 (t, J=7.2Hz, 3H), 1.86-1.96 (m, 1H), 2.04-2.12 (m, 1H), 2.65-2.77 (m, 2H), 2.84 (d, J=6.0Hz, 1H), 3.79 (s, 3H), 4.14-4.19 (m, 1H), 4.22 (q, J=7.2Hz, 2H), 6.82-7.15 (m, 4H).
13C NMR (100MHz, CDCl
3): 14.2,30.1,36.2,55.2,61.6,69.7,113.8,129.5,133.2,157.9,175.3.
Embodiment 9
Asymmetric catalytic hydrogenation preparation (R)-4-(the 3-chlorine)-phenyl-2-3-hydroxyethyl butyrate of 4-(3-chlorine)-phenyl-2-ketobutyric acid
Operation is as described in the embodiment 5,6, uses [RuCl (benzene) (R)-SunPhos] Cl as catalyzer, (R)-4-(3-chlorine)-phenyl-2-3-hydroxyethyl butyrate: crude product ee:90.2%; Refining back yield: 89%; Ee:99.0%.Nuclear magnetic data:
1H NMR (400MHz, CDCl
3): 1.30 (t, J=7.2Hz, 3H), 1.89-1.98 (m, 1H), 2.06-2.15 (m, 1H), 2.70-2.79 (m, 2H), 2.90 (d, J=4.8Hz, 1H), 4.14-4.18 (m, 1H), 4.22 (q, J=7.2Hz, 2H), 7.08-7.24 (m, 4H).
13CNMR (100MHz, CDCl
3): 14.4,30.9,35.8,62.0,69.7,126.4,127.0,128.9,129.9,134.3,143.5,175.2.
Embodiment 10
Asymmetric catalytic hydrogenation preparation (R)-4-(the 4-chlorine)-phenyl-2-3-hydroxyethyl butyrate of 4-(4-chlorine)-phenyl-2-ketobutyric acid
Operation is as described in the embodiment 5,6, uses [RuCl (benzene) (R)-SunPhos] Cl as catalyzer, (R)-4-(4-chlorine)-phenyl-2-3-hydroxyethyl butyrate: crude product ee:89.8%; Refining back yield 89%; Ee:99.0%.Nuclear magnetic data:
1HNMR (400MHz, CDCl
3): 1.29 (t, J=7.2Hz, 3H), 1.87-1.96 (m, 1H), 2.04-2.13 (m, 1H), 2.67-2.80 (m, 2H), 2.88 (d, J=5.2Hz, 1H), 4.13-4.17 (m, 1H), 4.22 (q, J=7.2Hz, 2H), 7.12-7.27 (m, 4H).
13C NMR (100MHz, CDCl
3): 14.4,30.6,36.0,62.0,69.7,128.7,129.7,131.9,139.8,175.3.
Embodiment 11
Asymmetric catalytic hydrogenation preparation (R)-4-(2, the 4-dichloro)-phenyl-2-3-hydroxyethyl butyrate of 4-(2, the 4-dichloro)-phenyl-2-ketobutyric acid
Operation is as described in the embodiment 5,6, uses [RuCl (benzene) (R)-SunPhos] Cl as catalyzer, (R)-4-(2, the 4-dichloro)-phenyl-2-3-hydroxyethyl butyrate: crude product ee:89.5%; Refining back yield: 88%; Ee:99.0%.Nuclear magnetic data:
1H NMR (400MHz, CDCl
3): 1.30 (t, J=7.2Hz, 3H), 1.89-1.98 (m, 1H), 2.04-2.13 (m, 1H), 2.82-2.86 (m, 2H), 2.90 (d, J=5.2Hz, 1H), 4.16-4.23 (m, 1H), 4.23 (q, J=7.2Hz, 2H), 7.17-7.36 (m, 3H).
13C NMR (100MHz, CDCl
3): 14.2,28.5,33.8,61.9,69.6,127.1,129.3,131.5,132.5,134.7,137.4,175.0.
Embodiment 12
4-(asymmetric catalytic hydrogenation preparation (the R)-4-of 5-benzo [1,3] dioxy-yl)-phenyl-2-ketobutyric acid (5-benzo [1,3] dioxy-yl)-phenyl-2-3-hydroxyethyl butyrate
Operation is as described in the embodiment 5,6, uses [RuCl (benzene) (R)-SunPhos] Cl as catalyzer, (R)-4-(5-benzo [1,3] dioxy-yl)-phenyl-2-3-hydroxyethyl butyrate: crude product ee:92.5%; Refining back yield: 90%; Ee:99.0%.Nuclear magnetic data:
1H NMR (400MHz, CDCl
3): 1.30 (t, J=7.2Hz, 3H), 1.84-1.94 (m, 1H), 2.02-2.11 (m, 1H), 2.62-2.75 (m, 2H), 2.85 (d, J=5.6Hz, 1H), 4.14-4.18 (m, 1H), 4.23 (q, J=7.2Hz, 2H), 5.92 (s, 2H), 6.65-6.75 (m, 3H).
13C NMR (100MHz, CDCl
3): 14.4,31.0,36.4,62.0,69.7,101.0,108.4,109.2,121.6,135.2,146.0,147.8,175.4..
Claims (10)
1. the preparation method of an optically pure 4-aryl-2-hydroxy-butyric ester, it is characterized in that, in organic ethers or alcoholic solvent, 4-aryl-2-ketobutyric acid is in the presence of the ruthenium complex of biaryl standard shaft chiral phosphine ligand and acid additives common, through asymmetric catalytic hydrogenation reaction and esterification, prepare optically pure 4-aryl-2-hydroxybutyric acid, obtain optically pure 4-aryl 2-butyric ester through over-churning;
Described solvent is a kind of of tetrahydrofuran (THF), methyltetrahydrofuran, dioxane, dioxolane, glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol bisthioglycolate propyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diisopropyl ether and di-n-butyl ether organic ether kind solvent;
Described aryl is phenyl, naphthyl, substituted-phenyl or substituted naphthyl;
The substituted radical of described substituted-phenyl or substituted naphthyl is alkyl, alkoxyl group, halogen, amino or sulfydryl;
Described additive is organic sulfonic acids such as Hydrogen bromide, hydroiodic acid HI, hydrochloric acid, sulfuric acid, phosphoric acid, fluoroboric acid, boric acid, trifluoracetic acid or tosic acid;
Described phosphine ligand L is SunPhos, SegPhos, BINAP, DifluroPhos biaryl standard shaft chiral phosphine ligand, and its molecular structural formula is as follows:
SunPhos SegPhos BINAP DifluroPhos
Described catalyzer is: RuLCl
2, [RuCl (benzene) (L)] Cl, [RuBr (benzene) (L)] Br, [RuCl (cymene) (L)] Cl, RuLCl
2(DMF)
m, [NH
2Me
2]
+[(RuClL)
2(μ-Cl
3)];
Described asymmetric catalytic hydrogenation reaction and esterification, reaction formula is as follows:
2. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1 is characterized in that, described solvent is a kind of of methyl alcohol, ethanol, Virahol or trimethyl carbinol organic liquid alcoholic solvent.
3. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1, it is characterized in that described solvent is the mixed solvent of tetrahydrofuran (THF), methyltetrahydrofuran, dioxane, dioxolane, glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol bisthioglycolate propyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diisopropyl ether, di-n-butyl ether ethers and methyl alcohol, ethanol, Virahol, trimethyl carbinol alcohols two classes.
4. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1 is characterized in that, described additive is a Hydrogen bromide.
5. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1 is characterized in that, described phosphine ligand L is SunPhos.
6. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1 is characterized in that, described catalyzer is that the complex compound of ruthenium and phosphine part is [RuCl (benzene) (R)-SunPhos] Cl.
7. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1 is characterized in that, carries out during temperature that described being reflected at-20 is ℃-120 ℃.
8. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1 is characterized in that, described reaction mol ratio is that 4-aryl-2-ketobutyric acid/catalyzer is 100/1 to 50000/1.
9. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 8 is characterized in that; Described reaction mol ratio is that 4-aryl-2-ketobutyric acid/catalyzer is 10000/1.
10. the preparation method of optically pure 4-aryl-2-hydroxy-butyric ester according to claim 1 is characterized in that, described ester group is C
1-C
6Straight chained alkyl or the alkyl or the substituted alkyl of side chain are arranged.
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| CN105669423A (en) * | 2016-01-08 | 2016-06-15 | 江西科技师范大学 | New synthesis method of two enantiomers of 4-(4-(benzyloxy)phenyl)-2-hydroxybutyric acid |
| CN106431919A (en) * | 2016-09-08 | 2017-02-22 | 南京大学 | Synthesis method of photoactive 2-aryl propionic acid and derivatives thereof |
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| CN101391960A (en) * | 2008-11-06 | 2009-03-25 | 上海交通大学 | Method for preparing optically pure 2-hydroxyl-4-aryl-butyric ether |
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| CN101391960A (en) * | 2008-11-06 | 2009-03-25 | 上海交通大学 | Method for preparing optically pure 2-hydroxyl-4-aryl-butyric ether |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105669423A (en) * | 2016-01-08 | 2016-06-15 | 江西科技师范大学 | New synthesis method of two enantiomers of 4-(4-(benzyloxy)phenyl)-2-hydroxybutyric acid |
| CN105669423B (en) * | 2016-01-08 | 2018-06-29 | 江西科技师范大学 | The novel synthesis of two kinds of enantiomters of 4- (4- (benzyloxy) phenyl) -2- hydroxybutyric acids |
| CN106431919A (en) * | 2016-09-08 | 2017-02-22 | 南京大学 | Synthesis method of photoactive 2-aryl propionic acid and derivatives thereof |
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| CN101914023B (en) | 2013-05-22 |
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