CN102786407B - Method of preparing (2R)-2-propyl caprylic acid - Google Patents

Method of preparing (2R)-2-propyl caprylic acid Download PDF

Info

Publication number
CN102786407B
CN102786407B CN201210289940.8A CN201210289940A CN102786407B CN 102786407 B CN102786407 B CN 102786407B CN 201210289940 A CN201210289940 A CN 201210289940A CN 102786407 B CN102786407 B CN 102786407B
Authority
CN
China
Prior art keywords
compound
oxazolidine
reaction
propyl
phenylimide
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.)
Expired - Fee Related
Application number
CN201210289940.8A
Other languages
Chinese (zh)
Other versions
CN102786407A (en
Inventor
卢翠芬
杨桂春
陈祖兴
苏杭
张隆铎
卢桃桃
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hubei University
Original Assignee
Hubei University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hubei University filed Critical Hubei University
Priority to CN201210289940.8A priority Critical patent/CN102786407B/en
Publication of CN102786407A publication Critical patent/CN102786407A/en
Application granted granted Critical
Publication of CN102786407B publication Critical patent/CN102786407B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

Landscapes

  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The invention relates to a method of preparing (2R)-2-propyl caprylic acid. The method comprises the following steps of: reacting (4R)-benzyl-1,3-oxazolidine-2-phenylimide with caprylyl chloride under the action of triethylamine and 4-dimethylamino-pyridine to obtain (4R)-benyl-N-capryloyl-1,3-oxazolidine-2-phenylimide; reacting the obtained compound with iodopropane to obtain (2'R, 4R)-benzyl-N-(2-propylcaprylyl)-1,3-oxazolidine-2-phenylimide; and releasing to obtain the (2R)-2-propyl caprylic acid. According to the method, chiral oxazolidine-2-phenylimide is used as a chiral auxiliary reagent to induce asymmetric alkylation reaction to synthesize the (2R)-2-propyl caprylic acid; the optical purity of the (2R)-2-propyl caprylic acid is greater than 98.7 percent e.e.; and the used chiral oxazolidine-2-phenylimide, serving as the chiral auxiliary reagent, can be recycled. The method has the advantages of feasible reaction line, simple post-treatment, capability of recycling the chiral auxiliary reagent, no need of catalytic reduction step and capability of avoiding recemization of a product.

Description

One is prepared the method for (2R)-2-propyloctanoic acid
Technical field
The present invention relates to one and prepare the method for (2R)-2-propyloctanoic acid, especially the method as synthetic (the 2R)-2-propyloctanoic acid of chiral auxiliary reagent induction asymmetric alkylation reaction with Shou oxazolidine-2-benzene imines.
Optically active (the 2R)-2-of having of preparing with this method propyloctanoic acid can be used as medicine.
Background technology
The not same-action of enantiomers of chiral drugs in physiological process is more and more familiar with by people, and the effective constituent of many chiral drugs is the one in enantiomorph, and other enantiomorph is invalid or poisonous.Thereby, in order to develop safe drugs, just need to replace racemoid with thering is optically active compound, and to require optical purity be almost 100%.Asymmetric synthesis is to obtain to have one of important method of optical activity chirality material, and a large amount of method of asymmetric synthesis being widely used in industrial production, has greatly promoted the development of pharmaceutical industry.
Utilizing chiral auxiliary reagent to carry out asymmetric synthesis is a kind of important method of asymmetric synthesis.Its action principle is first the chiral auxiliary reagent with chirality to be connected by chemical bond with achirality material, then induce asymmetric reaction, utilize the sterically hindered induction of chiral auxiliary reagent to produce new chiral centre, finally again chiral auxiliary reagent is escaped, obtain new chiral product.Shou oxazolidine-2-benzene imines is the novel chiral auxiliary reagent of a class, and the reaction of induction asymmetric alkylation, shows good asymmetric induction effect, has good chemical yield.
(2R)-2-propyloctanoic acid can be used as medicine, for example: at the example 7(33 of JP-A-7-316092 (EP632008)) in racemic modification that to have described as treatment or prevention be (2R)-2-propyloctanoic acid due to the medicament of the unusual neurodegenerative disease causing of Astrocytic function.Further research is found, the compound with optically active R-configuration shows strong drug effect, and toxicity is less.Therefore, carry out again afterwards various research and a kind ofly can effectively obtain the method with optically active R configuration of compound to find out.
(2R) synthetic method of-2-propyloctanoic acid mainly contains chiral separation method and dissymmetric synthesis.For example, in JP-A-8-291106, JP-7-98328, utilization has optically active amine the sad optical resolution of carrying out of racemic 2-(2-propynyl) is obtained having optically active salt, thereby it is sad that the salt obtaining obtains having optically active (2S)-2-(2-propynyl) with acid treatment, and then carry out catalytic reduction reaction and obtain required product.Chiral separation method need to split 5 times just can obtain the product that optical purity is 90%ee, and productive rate is very low.
In addition, in WO9958513, EP1078921, US6333415, EP1153910, WO0048982, WO0351852, CN00804013.3, sad or (2S)-2-(2-propynyl) is sad prepares (2 by catalytic reduction (2S)-2-(2-propenyl) r)-2-propyloctanoic acid.In above-mentioned specification sheets, (2S)-2-(2-propenyl) is sad or (2S)-2-(2-propynyl) is sad obtains by freeing chiral auxiliary reagent after camphor sultam or the reaction of chiral oxazolidinone chiral auxiliary reagent induction asymmetric alkylation, in this process, expensive chiral auxiliary reagent can not recycling, and catalytic reduction reaction can cause racemization, inevitably produce the by product of a small amount of S configuration.
In the present invention, we carry out asymmetric alkylation with Shou oxazolidine-2-benzene imines cheap and easy to get as chiral auxiliary reagent and iodopropane and react, after freeing chiral auxiliary reagent, obtain having optically active (2R)-2-propyloctanoic acid, do not need further catalytic reduction step, realized the recycling use of chiral auxiliary reagent simultaneously.
Summary of the invention
The object of the invention is to, provide one to prepare the method for (2R)-2-propyloctanoic acid, the method is the asymmetric synthesis of chiral auxiliary reagent induction, reaction scheme is feasible, aftertreatment is simple, chiral auxiliary reagent is recyclable to be recycled, and does not need catalytic reduction step, avoids product racemization.
Technical scheme provided by the invention is that one is prepared (2R)-2-propyloctanoic acid (compound 1)method, the method comprises the following steps:
The first step: in organic solvent, (4R)-benzyl-1,3-oxazolidine-2-benzene imines (compound 2) under triethylamine and DMAP effect, react with capryl(yl)chloride and obtain (4R)-benzyl-N-capryloyl-1,3-oxazolidine-2-benzene imines (compound 3), temperature of reaction is 0～25 ℃, and the reaction times is 0.5～2h, and the mol ratio of above-claimed cpd is compound 2:triethylamine: DMAP: capryl(yl)chloride=1:1～1.5:0.1～0.3:1～1.5;
Second step: in organic solvent, compound 3under organic bases effect ,react with iodopropane and obtain (2 ' R, 4R)-benzyl-N-(2-propyl group capryloyl)-1,3-oxazolidine-2-benzene imines (compound 4), temperature of reaction is-78～0 ℃, and the reaction times is 2～5h, and the mol ratio of above-claimed cpd is compound 3:organic bases: iodopropane=1:1～1.5:2～4;
The 3rd step: in mixed solvent, compound 4under lithium hydroxide and hydrogen peroxide effect, free and obtain compound 1, temperature of reaction is 0～25 ℃, and the reaction times is 24～48h, and the mol ratio of above-claimed cpd is compound 4:lithium hydroxide :hydrogen peroxide=1:1.5～3:3～6;
Above-claimed cpd 1, 2, 3, 4there is following structural formula:
Figure 767711DEST_PATH_IMAGE001
Described organic solvent is methylene dichloride, trichloromethane, N, N '-dimethyl formamide, tetrahydrofuran (THF), ethyl acetate, acetonitrile or dioxane.
Described organic bases is n-Butyl Lithium, diisopropylamine lithium, hexamethyldisilane base amine sodium, hexamethyldisilane base amine potassium or hexamethyldisilane base amine lithium.
Described mixed solvent is N, the mixed solvent of N '-dimethyl formamide, tetrahydrofuran (THF) or dioxane and water, and volume ratio is 3～5:1.
Above-mentioned reaction process is represented by following reaction formula:
Figure 327569DEST_PATH_IMAGE002
?the present invention proposes one and prepare (2R)-2-propyloctanoic acid 1method.With Shou oxazolidine-2-benzene imines, as synthetic (the 2R)-2-propyloctanoic acid of chiral auxiliary reagent induction asymmetric alkylation reaction, obtain the chiral drug of high-optical-purity, its optical purity is greater than 98.7 %e.e.Reaction scheme of the present invention is feasible, and aftertreatment is simple, and recyclable the recycling of Shou oxazolidine-2-benzene imines chiral auxiliary reagent of using, does not need catalytic reduction step, avoids product racemization.
Embodiment
By following examples, will contribute to understand the present invention, but not limit content of the present invention.
Embodiment 1
(4R)-benzyl-1,3-oxazolidine-2-benzene imines (5.0 g, 19.82 mmol) be dissolved in dry methylene dichloride (50 mL), add DMAP (0.72 g, 5.94 mmol) and dry triethylamine (4.36 mL, 29.73 mmol), 0 ℃ with 1 drop/sec of dichloromethane solution (10 mL) that dropwise drips capryl(yl)chloride (5.07 mL, 29.73 mmol).Continue reaction 2 h, add saturated ammonium chloride solution cancellation reaction, separatory, dichloromethane extraction for water (3 × 20 mL).Merge organic phase; respectively by saturated sodium bicarbonate solution, distilled water, saturated common salt washing organic phase (3 × 20 mL); collect organic phase; anhydrous magnesium sulfate drying, filters, except after desolventizing through column chromatography (ethyl acetate: sherwood oil=1:20; volume ratio) separating-purifying obtains faint yellow oily matter; be product (4R)-benzyl-N-capryloyl-1,3-oxazolidine-2-benzene imines (6.8 g, 90.7%).[
Figure 189050DEST_PATH_IMAGE004
] D 25=?-40.2?(c?1.2,?CH 2Cl 2);?IR?(NaCl):? υ1704,?1684,?1595,?1454,?1231,?748,?701?cm -1;? 1H?NMR?(600?MHz,?CDCl 3):? δ?7.32-6.91(10H,?m),?4.78-4.75(1H,?m),?4.14-4.11(2H,?m),?3.22-3.14(2H,?m),?3.09(1H,?dd,? J=6.6,?8.4?Hz),?2.83(1H,?dd,? J=9.6,?13.8?Hz),?1.73-1.69(2H,?m),?1.30-1.26?(8H,?m),?0.86(3H,?t,? J=7.2?Hz);? 13C?NMR?(150MHz,?CDCl 3):? δ?173.3,?145.6,?135.9,?129.5,?128.7,?128.5,?127.0,?123.3,?122.6,?67.7,?55.9,?37.6,?36.3,?34.1,?31,6,?29.1,?24.6,?22.5,?14.0。
Embodiment 2
(4R)-benzyl-1,3-oxazolidine-2-benzene imines (5.0 g, 19.82 mmol) be dissolved in dry methylene dichloride (50 mL), add DMAP (0.24 g, 1.98 mmol) and dry triethylamine (2.91 mL, 19.82 mmol), 25 ℃ with 1 drop/sec of dichloromethane solution (10 mL) that dropwise drips capryl(yl)chloride (3.38 mL, 19.82 mmol).Continue reaction 0.5 h, add saturated ammonium chloride solution cancellation reaction, separatory, dichloromethane extraction for water (3 × 20 mL).Merge organic phase; respectively by saturated sodium bicarbonate solution, distilled water, saturated common salt washing organic phase (3 × 20 mL); collect organic phase; anhydrous magnesium sulfate drying, filters, except after desolventizing through column chromatography (ethyl acetate: sherwood oil=1:20; volume ratio) separating-purifying obtains faint yellow oily matter; be product (4R)-benzyl-N-capryloyl-1,3-oxazolidine-2-benzene imines (6.3 g, 84.0%).[
Figure 409423DEST_PATH_IMAGE004
] D 25=?-40.2?(c?1.2,?CH 2Cl 2);?IR?(NaCl):? υ1704,?1684,?1595,?1454,?1231,?748,?701?cm -1;? 1H?NMR?(600?MHz,?CDCl 3):? δ?7.32-6.91(10H,?m),?4.78-4.75(1H,?m),?4.14-4.11(2H,?m),?3.22-3.14(2H,?m),?3.09(1H,?dd,? J=6.6,?8.4?Hz),?2.83(1H,?dd,? J=9.6,?13.8?Hz),?1.73-1.69(2H,?m),?1.30-1.26?(8H,?m),?0.86(3H,?t,? J=7.2?Hz);? 13C?NMR?(150MHz,?CDCl 3):? δ?173.3,?145.6,?135.9,?129.5,?128.7,?128.5,?127.0,?123.3,?122.6,?67.7,?55.9,?37.6,?36.3,?34.1,?31,6,?29.1,?24.6,?22.5,?14.0。
Figure 273605DEST_PATH_IMAGE005
Embodiment 3
(4R)-benzyl-N-capryloyl-1 being dried; 3-oxazolidine-2-benzene imines (3.2 g; 8.45 mmol) be dissolved in anhydrous tetrahydro furan (15 mL); pass into nitrogen, add hexamethyldisilane base amine sodium (6.36 mL, 12.67 mmol at-78 ℃; 2 M in hexane); after stirring 0.5 h, add iodopropane (3.32 mL, 33.8 mmol), maintain-78 ℃ of reaction 4h.Add saturated ammonium chloride solution cancellation reaction, concentrated, dichloromethane extraction (3 × 10 mL).Merge organic phase; saturated common salt water washing; anhydrous sodium sulfate drying; filter, except after desolventizing, through column chromatography (ethyl acetate: sherwood oil=1:30, volume ratio) separating-purifying, obtain faint yellow oily matter; be product (2 ' R; 4R)-benzyl-N-(2-propyl group capryloyl)-1,3-oxazolidine-2-benzene imines (3.04 g, 85.5 %).[
Figure 74202DEST_PATH_IMAGE004
] d 25=+56.25 (c 0.2, CH 2cl 2); De > 99% [HPLC, Chiralcel OJ-RH, MeCN – H 2o (80:20), flow velocity 1.0 mL/min, 254 nm]; IR (NaCl): υ1703,1682,1595,1455,1220,748,700 cm -1; 1h NMR (600 MHz, CDCl 3): δ7.33-6.95 (10H, m), 4.81-4.78 (1H, m), 4.36-4.32 (1H, m), 4.10-4.05 (2H, m), 3.25 (1H, dd, j=2.4,13.2 Hz), 2.80 (1H, dd, j=9.6,13.2 Hz), 1.52-1.49 (2H, m), 1.45-1.42 (2H, m), 1.29-1.24 (10H, m), 0.95 (3H, t, j=7.2 Hz), 0.86 (3H, t, j=6.0 Hz); 13c NMR (150 MHz, CDCl 3): δ176.8,145.8,136.0,129.5,128.7,128.5,127.0,123.3,122.6,67.4,56.2,42.1,37.7,34.6,32.3,31.7,29.4,27.4,22.5,20.4,14.3,14.0.
Embodiment 4
(4R)-benzyl-N-capryloyl-1 being dried; 3-oxazolidine-2-benzene imines (3.2 g; 8.45 mmol) be dissolved in anhydrous tetrahydro furan (15 mL); pass into nitrogen, add hexamethyldisilane base amine lithium (8.45 mL, 8.45 mmol at-78 ℃; 1 M in THF); after stirring 0.5 h, add iodopropane (1.66 mL, 16.9 mmol), after-78 ℃ of reaction 0.5 h, be warmed up to 0 ℃ and continue reaction 1h.Add saturated ammonium chloride solution cancellation reaction, concentrated, dichloromethane extraction (3 × 10 mL).Merge organic phase; saturated common salt water washing; anhydrous sodium sulfate drying; filter, except after desolventizing, through column chromatography (ethyl acetate: sherwood oil=1:30, volume ratio) separating-purifying, obtain faint yellow oily matter; be product (2 ' R; 4R)-benzyl-N-(2-propyl group capryloyl)-1,3-oxazolidine-2-benzene imines (2.83 g, 79.8 %).[ ] d 25=+56.25 (c 0.2, CH 2cl 2); De > 99% [HPLC, Chiralcel OJ-RH, MeCN – H 2o (80:20), flow velocity 1.0 mL/min, 254 nm]; IR (NaCl): υ1703,1682,1595,1455,1220,748,700 cm -1; 1h NMR (600 MHz, CDCl 3): δ7.33-6.95 (10H, m), 4.81-4.78 (1H, m), 4.36-4.32 (1H, m), 4.10-4.05 (2H, m), 3.25 (1H, dd, j=2.4,13.2 Hz), 2.80 (1H, dd, j=9.6,13.2 Hz), 1.52-1.49 (2H, m), 1.45-1.42 (2H, m), 1.29-1.24 (10H, m), 0.95 (3H, t, j=7.2 Hz), 0.86 (3H, t, j=6.0 Hz); 13c NMR (150 MHz, CDCl 3): δ176.8,145.8,136.0,129.5,128.7,128.5,127.0,123.3,122.6,67.4,56.2,42.1,37.7,34.6,32.3,31.7,29.4,27.4,22.5,20.4,14.3,14.0.
Embodiment 5
(2 ' R; 4R)-benzyl-N-(2-propyl group capryloyl)-1; 3-oxazolidine-2-benzene imines (2.1 g; 4.99 mmol) be dissolved in the mixed solvent (50 mL) of tetrahydrofuran (THF) and water (4:1, volume ratio), add successively lithium hydroxide (0.18 g at 25 ℃; 7.48 mmol) and hydrogen peroxide (1.72 mL; 14.97 mmol, 30%), 25 ℃ of reaction 24 h.Add sodium sulfite solution cancellation reaction, the concentrated tetrahydrofuran (THF) of removing, with sodium hydrogen carbonate solution tune pH to 9-10, dichloromethane extraction (3 × 10mL).Organic phase anhydrous magnesium sulfate drying, filters, except reclaiming (4R)-benzyl-1,3-oxazolidine-2-benzene imines (1.12 g, the rate of recovery 89.0%) after desolventizing.Water is adjusted pH to 1-2 with hydrochloric acid, ethyl acetate extraction (3 × 20 mL), merge organic phase, saturated common salt washing (3 × 20mL), anhydrous magnesium sulfate drying, filters, except after desolventizing through column chromatography (ethyl acetate: sherwood oil=1:10, volume ratio) separating-purifying obtains colorless oil, i.e. product (2R)-2-propyloctanoic acid (0.40 g, 43.0%).[
Figure 98154DEST_PATH_IMAGE004
] d 20=-5.9 (c 1.7, EtOH); Ee=98.7%, ee value is converted into corresponding phenacylate and records [HPLC, Chiralcel OJ-RH, MeCN – H by (2R)-propyloctanoic acid is reacted with bromoacetophenone 2o (60:40), flow velocity 0.5 mL/min, 244 nm]; IR (NaCl): υ1706,1419,944 cm -1; 1h NMR (600 MHz, CDCl 3): δ2.38-2.34 (1H, m), 1.64-1.59 (2H, m), 1.49-1.43 (2H, m), 1.38-1.26 (10H, m), 0.91 (3H, t, j=7.2 Hz), 0,87 (3H, t, j=6.6 Hz); 13c NMR (150 MHz, CDCl 3): δ183.0,45.2,34.2,32.0,31.5,29.1,27.2,22.5,20.4,13.9,13.8.
Embodiment 6
(2 ' R; 4R)-benzyl-N-(2-propyl group capryloyl)-1; 3-oxazolidine-2-benzene imines (2.1 g; 4.99 mmol) be dissolved in the mixed solvent (50 mL) of tetrahydrofuran (THF) and water (4:1, volume ratio), add successively lithium hydroxide (0.36 g at 0 ℃; 14.97 mmol) and hydrogen peroxide (3.44 mL; 29.94 mmol, 30%), 0 ℃ of reaction 48 h.Add sodium sulfite solution cancellation reaction, the concentrated tetrahydrofuran (THF) of removing, with sodium hydrogen carbonate solution tune pH to 9-10, dichloromethane extraction (3 × 10mL).Organic phase anhydrous magnesium sulfate drying, filters, except reclaiming (4R)-benzyl-1,3-oxazolidine-2-benzene imines (1.18 g, the rate of recovery 93.8%) after desolventizing.Water is adjusted pH to 1-2 with hydrochloric acid, ethyl acetate extraction (3 × 20 mL), merge organic phase, saturated common salt washing (3 × 20mL), anhydrous magnesium sulfate drying, filters, except after desolventizing through column chromatography (ethyl acetate: sherwood oil=1:10, volume ratio) separating-purifying obtains colorless oil, i.e. product (2R)-2-propyloctanoic acid (0.49 g, 52.6%).[
Figure 572997DEST_PATH_IMAGE004
] d 20=-6.0 (c 1.7, EtOH); Ee=99.2%, ee value is converted into corresponding phenacylate and records [HPLC, Chiralcel OJ-RH, MeCN – H by (2R)-propyloctanoic acid is reacted with bromoacetophenone 2o (60:40), flow velocity 0.5 mL/min, 244 nm]; IR (NaCl): υ1706,1419,944 cm -1; 1h NMR (600 MHz, CDCl 3): δ2.38-2.34 (1H, m), 1.64-1.59 (2H, m), 1.49-1.43 (2H, m), 1.38-1.26 (10H, m), 0.91 (3H, t, j=7.2 Hz), 0,87 (3H, t, j=6.6 Hz); 13c NMR (150 MHz, CDCl 3): δ183.0,45.2,34.2,32.0,31.5,29.1,27.2,22.5,20.4,13.9,13.8.

Claims (2)

1. prepare (2R)-2-propyloctanoic acid for one kind 1method, comprise the following steps:
The first step: in organic solvent, compound 2under triethylamine and DMAP effect, react and obtain compound with capryl(yl)chloride 3, temperature of reaction is 0～25 ℃, and the reaction times is 0.5～2h, and the mol ratio of above-claimed cpd is compound 2:triethylamine: DMAP: capryl(yl)chloride=1:1～1.5:0.1～0.3:1～1.5;
Second step: in organic solvent, compound 3under organic bases effect ,react and obtain compound with iodopropane 4, temperature of reaction is-78～0 ℃, and the reaction times is 2～5h, and the mol ratio of above-claimed cpd is compound 3:organic bases: iodopropane=1:1～1.5:2～4; Described organic bases is hexamethyldisilane base amine sodium or hexamethyldisilane base amine lithium;
The 3rd step: in mixed solvent, compound 4under lithium hydroxide and hydrogen peroxide effect, free and obtain compound 1, temperature of reaction is 0～25 ℃, and the reaction times is 24～48h, and the mol ratio of above-claimed cpd is compound 4:lithium hydroxide :hydrogen peroxide=1:1.5～3:3～6; Described mixed solvent is the mixed solvent of glycol dimethyl ether, tetrahydrofuran (THF) or dioxane and water, and volume ratio is 3～5:1;
Above-claimed cpd 1, 2, 3, 4there is following structural formula:
Figure 142910DEST_PATH_IMAGE001
Described organic solvent is methylene dichloride, 1,2-ethylene dichloride, tetrahydrofuran (THF), acetonitrile, glycol dimethyl ether, ethylene glycol diethyl ether or dioxane.
2. the method for claim 1, is characterized in that: recyclable the recycling of compound 2 Shou oxazolidine-2-benzene imines chiral auxiliary reagent of using.
CN201210289940.8A 2012-08-15 2012-08-15 Method of preparing (2R)-2-propyl caprylic acid Expired - Fee Related CN102786407B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201210289940.8A CN102786407B (en) 2012-08-15 2012-08-15 Method of preparing (2R)-2-propyl caprylic acid

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201210289940.8A CN102786407B (en) 2012-08-15 2012-08-15 Method of preparing (2R)-2-propyl caprylic acid

Publications (2)

Publication Number Publication Date
CN102786407A CN102786407A (en) 2012-11-21
CN102786407B true CN102786407B (en) 2014-04-16

Family

ID=47152016

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201210289940.8A Expired - Fee Related CN102786407B (en) 2012-08-15 2012-08-15 Method of preparing (2R)-2-propyl caprylic acid

Country Status (1)

Country Link
CN (1) CN102786407B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103483286B (en) * 2013-09-18 2015-03-11 湖北大学 Oxazolidine-2-phenyl imine derived from camphor and preparing method and application thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1341091A (en) * 1999-02-18 2002-03-20 小野药品工业株式会社 Process for preparation of (2R)-2-propyloctanoic acid

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1341091A (en) * 1999-02-18 2002-03-20 小野药品工业株式会社 Process for preparation of (2R)-2-propyloctanoic acid

Also Published As

Publication number Publication date
CN102786407A (en) 2012-11-21

Similar Documents

Publication Publication Date Title
Okamura et al. Organocatalytic asymmetric oxy-Michael addition to a γ-hydroxy-α, β-unsaturated thioester via hemiacetal intermediates
CN103333942B (en) A synthetic method for (R)-praziquantel
CN104341390A (en) Asymmetric synthesis method for botanical pesticide nicotine and anabasine
CN105198775A (en) Preparation method of chiral N-Boc biphenyl alaninol
CN102180823B (en) A kind of method of refining prolinamide
CN104447725A (en) Chiral compound comprising iminopyridyl oxazoline and preparation method thereof
CN104402718B (en) A kind of chiral allyl ester type compound and preparation method thereof
DE60102825T2 (en) KINETIC RACEMATING OF CHIRALER 2 AND 3 SUBSTITUTED CARBOXYLIC ACIDS
CN102786407B (en) Method of preparing (2R)-2-propyl caprylic acid
US8912345B2 (en) Method for preparing optically pure (−)-clausenamide compound
CN107602559B (en) A method of the asymmetric ciprofloxacin eye drops synthesis of chiral ternary carbocyclic nucleoside caused by Michael's addition
CN104557583B (en) A kind of method synthesizing γ-aminobutyric acid class chipal compounds
CN103183673A (en) Synthesizing method of (S,S)-2,8-diazabicyclo[4.3.0]nonane
CN103951821A (en) Polyethylene glycol-supported bis(S)-2-(4'-benzyloxy)-N-methyl ethane-1,2-diamine and preparation method and application thereof
CN102906064B (en) The manufacture method of (1R, 2S)-1-amino-2-vinylcyclopropanecaracidlic acidlic ester that optical purity has been improved
CN103601708B (en) Preparation method of prostaglandin medicine impurity
US9328079B2 (en) Process for producing optically active amine
CN105732648A (en) Nitrogen heterocyclic ring compound of pyrrolofuran and synthetic method
CN103787921B (en) A kind of method preparing trans 1, the 2-ring diamines of high-optical-purity
Yonezawa et al. Desymmetrization of meso-methylenecyclopropanes by a palladium-catalyzed asymmetric ring-opening bis (alkoxycarbonylation) reaction
CN105801518B (en) A kind of synthetic method of (S) -1-Boc-3- hydroxy piperidine
CN104788415A (en) Method for asymmetrically synthesizing 4-nitromethyl-3-benzyl-3,4-dihydrocoumarin derivative
CN101314559A (en) Preparation of aromatic chirality secondary alcohol compounds
CN104119302A (en) Chiral tetrahydrofuran compound as well as preparation method and dehydration product thereof
CN102627571A (en) Preparation and synthesis method for chiral ammonium salt

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
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20140416

Termination date: 20160815

CF01 Termination of patent right due to non-payment of annual fee