CN112939925A - Long-chain alkanoic acid derivative and preparation method and application thereof - Google Patents
Long-chain alkanoic acid derivative and preparation method and application thereof Download PDFInfo
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- 239000002253 acid Substances 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 18
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 18
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
- 239000000126 substance Substances 0.000 claims description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 39
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 36
- 238000005406 washing Methods 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- 239000002904 solvent Substances 0.000 claims description 30
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 27
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 26
- 238000003756 stirring Methods 0.000 claims description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 18
- 238000001816 cooling Methods 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 18
- 239000008213 purified water Substances 0.000 claims description 17
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 claims description 15
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 238000004537 pulping Methods 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000012266 salt solution Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 41
- 239000002994 raw material Substances 0.000 abstract description 25
- 239000003814 drug Substances 0.000 abstract description 6
- 238000010189 synthetic method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 30
- 239000001257 hydrogen Substances 0.000 description 30
- 229910052739 hydrogen Inorganic materials 0.000 description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- 239000000047 product Substances 0.000 description 22
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 19
- 239000012535 impurity Substances 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 18
- 238000001819 mass spectrum Methods 0.000 description 16
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 238000004949 mass spectrometry Methods 0.000 description 12
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 238000002390 rotary evaporation Methods 0.000 description 12
- 238000009833 condensation Methods 0.000 description 9
- 230000005494 condensation Effects 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 235000021314 Palmitic acid Nutrition 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ASXKHYPKFDCKKV-UHFFFAOYSA-N 2-methyl-1,4-dioxepane-5,7-dione Chemical compound CC1COC(=O)CC(=O)O1 ASXKHYPKFDCKKV-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A long-chain alkanoic acid derivative and its preparation method and use, in the field of organic synthesis technology, regard long-chain hydroxy alkanoic acid derivative as raw materials, reduce under the condition that sodium borohydride exists, get long-chain alkanoic acid derivative, the invention adopts a new synthetic route, has reduced the cost of raw materials, the synthetic method has mild reaction condition, simple technological operation, characteristic such as being high of production efficiency, the long-chain alkanoic acid derivative is regarded as the midbody that the medicine is synthesized, have good application prospects.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a long-chain alkanoic acid derivative, and a preparation method and application thereof.
Background
The long-chain alkanoic acid derivatives are mostly important intermediates in organic synthesis, and are particularly important intermediates for synthesizing important medicines in the field of medicines.
The long-chain alkyl diacid mono-tert-butyl ester is an important intermediate for medical synthesis, wherein the octadecyl diacid mono-tert-butyl ester is used as an intermediate for synthesizing the somaglutide, the somaglutide is an analogue of glucagon-like peptide-1 (GLP-1), the application of the long-chain alkyl diacid mono-tert-butyl ester enables the treatment of diabetes to be developed in a breakthrough manner, but the octadecyl diacid mono-tert-butyl ester is expensive in price, the raw material for synthesizing the substance is expensive, and the synthesis difficulty is large, so that a proper raw material needs to be searched for solving the problems of high cost and great difficulty in the synthesis process of the octadecyl diacid mono-tert-butyl ester.
The long-chain alkanoic acid derivative is used as an important medical synthesis intermediate and can be used for synthesizing expensive long-chain alkyl diacid mono-tert-butyl ester. However, the prior art lacks a research on preparing long-chain alkyl diacid mono-tert-butyl ester by using long-chain alkanoic acid derivatives as raw materials, and lacks related reports aiming at the lack of the research on the long-chain alkanoic acid derivatives.
Disclosure of Invention
In view of the above, there is a need to provide a long-chain alkanoic acid derivative, a preparation method and applications thereof to solve the above problems.
The invention provides a long-chain alkanoic acid derivative, a preparation method and application thereof, wherein the long-chain alkanoic acid derivative shown as a formula D is prepared from a long-chain hydroxy alkanoic acid derivative
Wherein n is an integer of 0 or more.
In order to achieve the purpose, the invention is realized according to the following technical scheme:
a preparation method of a long-chain alkanoic acid derivative comprises the following steps:
reacting the long-chain hydroxy alkanoic acid derivative shown as E in the presence of sodium borohydride to prepare a long-chain alkanoic acid derivative shown as D, wherein in the following equation, n is an integer greater than or equal to 0;
preferably, the specific steps for producing D by the reaction of E are as follows:
and E, adding dichloromethane for dissolving, cooling to-5 ℃, adding acetic acid for stirring, adding sodium borohydride for reacting for 1-2 hours, extracting twice with a saturated sodium bicarbonate solution, washing with purified water, then with saturated salt solution, drying with anhydrous sodium sulfate, and pulping with methyl tert-butyl ether as a solvent to obtain D.
Preferably, in the specific step of preparing D from E, the molar ratio of E to acetic acid is 1: 8-15.
Preferably, in the specific step of preparing D by E, the molar ratio of E to sodium borohydride is 1: 1 to 5.
Preferably, the preparation method of the long-chain alkanoic acid derivative further comprises the following steps:
condensing the long-chain alkyl diacid and isopropylidene malonate shown as B' to prepare the long-chain hydroxy alkanoic acid derivative shown as E, wherein n is an integer which is more than or equal to 0 in the following formula;
preferably, the specific steps for preparing C by reacting A' with F are as follows:
and mixing A 'and F, adding dichloromethane for dissolving, cooling to-10-0 ℃ under the protection of inert gas, sequentially adding a catalyst 4-dimethylaminopyridine and a condensing agent N, N' -diisopropylcarbodiimide, reacting for 8-16 hours, extracting twice with a citric acid aqueous solution, washing with purified water, washing with saturated salt water, drying with anhydrous sodium sulfate, and pulping with methyl tert-butyl ether as a solvent to obtain E.
Preferably, in the specific step of preparing C by reacting A 'with F, the molar ratio of A' to F is 1: 1 to 1.3.
Preferably, in the specific step of preparing C by reacting A ' with F, the molar ratio of A ' to N, N ' -diisopropylcarbodiimide is 1: 1 to 1.3.
Preferably, in the specific step of preparing C by reacting A 'with F, the molar ratio of A' to 4-dimethylaminopyridine is 1: 1 to 2.
Preferably, n in the equation for the reaction of D, E to form D and the reaction of A' to form E is an integer of 6 or more.
Preferably, n-6 or n-7 in the equation for the reaction of D, E to form D and a' to form E.
Preferably, the long-chain alkanoic acid derivative is used as a synthesis intermediate in medical synthesis.
According to the technical scheme, the invention provides the long-chain alkanoic acid derivative and the preparation method thereof, and the long-chain alkanoic acid derivative has the following beneficial effects: the long-chain alkyl acid derivative is prepared by reducing the long-chain hydroxy alkyl acid derivative in the presence of sodium borohydride, the reaction process is simple, the conditions are mild, the operation is safe and easy, the production efficiency is high, and a route suitable for industrial production is created.
The long-chain alkanoic acid derivative provided by the invention is used as an intermediate for medicine synthesis and is used for synthesizing important medicine products.
Drawings
FIG. 1 is a drawing showing the preparation of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-enyl) -14-hydroxytetradecanoic acid prepared in example 1, example 2 and example 31H NMR spectrum.
FIG. 2 is a mass spectrum of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-enyl) -14-hydroxytetradecanoic acid prepared in example 1, example 2 and example 3.
FIG. 3 shows the reaction product of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid prepared in example 1, example 2 and example 31H NMR spectrum.
FIG. 4 is a mass spectrum of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid prepared in example 1, example 2 and example 3.
FIG. 5 is a drawing showing the preparation of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-enyl) -16-hydroxyhexadecanoic acid prepared in example 4, example 5 and example 61H NMR spectrum.
FIG. 6 is a mass spectrum of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-enyl) -16-hydroxyhexadecanoic acid prepared in example 4, example 5 and example 6.
FIG. 7 shows the preparation of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-) hexadecanoic acid prepared in example 4, example 5 and example 61H NMR spectrum.
FIG. 8 is a mass spectrum of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-) hexadecanoic acid prepared in example 4, example 5 and example 6.
Detailed Description
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following examples are briefly introduced, and the experimental methods without specifying specific conditions in the following examples are performed according to conventional methods and conditions.
The technical solutions and effects of the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings of the present invention.
A preparation method of a long-chain alkanoic acid derivative comprises the following steps:
reacting the long-chain hydroxy alkanoic acid derivative shown as E in the presence of sodium borohydride to prepare a long-chain alkanoic acid derivative shown as D, wherein in the following equation, n is an integer greater than or equal to 0;
preferably, the specific steps for producing D from E are as follows:
and E, adding dichloromethane for dissolving, cooling to-5 ℃, adding acetic acid for stirring, adding sodium borohydride for reacting for 1-2 hours, extracting twice with a saturated sodium bicarbonate solution, washing with purified water, then with saturated salt solution, drying with anhydrous sodium sulfate, and pulping with methyl tert-butyl ether as a solvent to obtain D.
Preferably, in the specific step of preparing D from E, the molar ratio of E to acetic acid is 1: 8-15, optimally, the molar ratio of E to acetic acid is 1: 10.
preferably, in the specific step of preparing D by E, the molar ratio of E to sodium borohydride is 1: 1-5, optimally, the molar ratio of E to sodium borohydride is 1: 3.
preferably, the preparation method of the long-chain alkanoic acid derivative further comprises the following steps:
condensing the long-chain alkyl diacid and isopropylidene malonate shown as B' to prepare the long-chain hydroxy alkanoic acid derivative shown as E, wherein n is an integer which is more than or equal to 0 in the following formula;
preferably, the specific steps for preparing C by reacting A' with F are as follows:
and mixing A 'and F, adding dichloromethane for dissolving, cooling to-10-0 ℃ under the protection of inert gas, sequentially adding a catalyst 4-dimethylaminopyridine and a condensing agent N, N' -diisopropylcarbodiimide, reacting for 8-16 hours, extracting twice with a citric acid aqueous solution, washing with purified water, washing with saturated salt water, drying with anhydrous sodium sulfate, and pulping with methyl tert-butyl ether as a solvent to obtain E.
Preferably, in the specific step of preparing C by reacting A 'with F, the molar ratio of A' to F is 1: 1-1.3 optimally, the molar ratio of A' to F is 1: 1.1.
preferably, in the specific step of preparing C by reacting A ' with F, the molar ratio of A ' to N, N ' -diisopropylcarbodiimide is 1: 1 to 1.3, and optimally, the molar ratio of A 'to N, N' -diisopropylcarbodiimide is 1: 1.1.
preferably, in the specific step of preparing C by reacting A 'with F, the molar ratio of A' to 4-dimethylaminopyridine is 1: 1-2, optimally, the molar ratio of A' to 4-dimethylamino pyridine is 1: 1.5.
preferably, in the formula in which D and E react to form D and a' react to form E, n is an integer of 6 or more, and most preferably, n is 6 or 7.
Preferably, the long-chain alkanoic acid derivative is used as a synthetic intermediate in the synthesis of a medicine.
The long-chain alkyl diacid is obtained by condensing the low-chain alkyl diacid and the isopropylidene malonate, and the method has mild reaction conditions, is safe and easy to operate, and creates a route suitable for industrial production. The long-chain alkanoic acid derivative is used as an intermediate for medical synthesis, and has high application value and economic value.
The technical scheme and technical effects of the invention are further explained by the specific examples below.
Example 1
Tetradecyl diacid is used as a raw material to prepare a tetradecyl acid derivative:
(1) condensation of tetradecyl diacid and isopropylidene malonate to prepare 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid
The specific reaction process is as follows:
under the protection of nitrogen, respectively adding 20g (77mmol) of tetradecyl diacid, 11.1g (77mmol) of isopropylidene malonate and 400ml of dichloromethane into a reaction bottle, stirring, cooling to-2 to-6 ℃, adding 9.4g (77mmol) of 4-dimethylaminopyridine, reacting for 8 to 12min, then adding 9.7g (77mmol) of N, N' -diisopropylcarbodiimide, moving to room temperature for reacting for 12h, extracting the post-treatment with 10% citric acid aqueous solution (200ml) twice, purifying (200ml) water, washing with saturated saline water (200ml), and drying the organic phase with anhydrous sodium sulfate (20 g); the solvent was removed by rotary evaporation to give crude 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-enyl) -14-hydroxytetradecanoic acid, which was slurried with methyl tert-butyl ether (50ml) and was calculated to give a yield of 86%.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIG. 1-2.
As can be seen from fig. 1:1h NMR (400MHz, CDCl3) δ 15.28(s,1H), 3.08-3.03 (m,2H), 1.75-1.66 (m,10H),1.27(d, J ═ 14.3Hz,14H),1.16(d, J ═ 6.5Hz,4H), where chemical shift 7.26 is a deuterated chloroform solvent peak, hydrogen on carboxyl group with chemical shift around 11 is not shown, peak with chemical shift 0 is for calibration, negligible, chemical shifts 3.8 and 2.35 are impurity peaks, suspected of being an impurity intermediate with incomplete condensation or a raw material peak with incomplete reaction;
as can be seen from fig. 2: the molecular weight of the compound is 384.46, ES-looks for a hydrogen reduction peak 383.28.
(2) Preparation of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid by reduction of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid
The specific reaction process is as follows:
adding 15g (39mmol) of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid into a reaction bottle under the protection of nitrogen, adding dichloromethane, stirring for dissolving, cooling to 2-0 ℃, adding 18.9g (312mmol) of acetic acid, stirring, adding 1.5g (39mmol) of sodium borohydride, continuing to react for 2-3 h, extracting the reaction solution twice by using saturated sodium bicarbonate (150ml), washing once by using purified water (150ml), washing by using saturated saline water (150ml), and drying an organic phase by using anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid; the crude product was slurried with methyl tert-butyl ether (35ml) to give the product in 46% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively; wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 3 to 4.
As can be seen from fig. 3:1h NMR (400MHz, CDCl3) δ 3.49(t, J ═ 5.0Hz,1H),2.16 to 2.04(m,2H),1.75(dd, J ═ 18.9,8.4Hz,8H),1.44(dd, J ═ 10.2,5.7Hz,2H),1.33 to 1.17(m,20H), where chemical shift 7.26 is a deuterated chloroform solvent peak, chemical shift 0 is a peak for calibration, negligible, chemical shift 11 is not shown for hydrogen on the carboxyl group, chemical shift 15.3 is a peak for hydrogen on the enol bond on the incompletely reduced raw material, chemical shifts 3.1 and 3.8 are impurity peaks, suspected of incompletely reduced impurity intermediates or incompletely reduced raw material peaks;
as can be seen from fig. 4: the molecular weight of the compound is 370.48, ES-looks for a hydrogen reduction peak 369.26.
Example 2
Tetradecyl diacid is used as a raw material to prepare a tetradecyl acid derivative:
(1) condensation of tetradecyl diacid and isopropylidene malonate to prepare 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid
The specific reaction process is as follows:
under the protection of nitrogen, respectively adding 20g (77mmol) of tetradecyl diacid, 12.2g (84.7mmol) of isopropylidene malonate and 400ml of dichloromethane into a reaction bottle, stirring, cooling to-2 to-6 ℃, adding 14g (115.5mmol) of 4-dimethylaminopyridine, reacting for 8-12 min, then adding 10.7g (84.7mmol) of N, N' -diisopropylcarbodiimide, moving to room temperature for reacting for 12h, extracting the post-treatment with 10% citric acid aqueous solution (200ml) twice, washing with purified water (200ml) once, washing with saturated saline water (200ml), and drying the organic phase with anhydrous sodium sulfate (20 g); the solvent was removed by rotary evaporation to give crude 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-enyl) -14-hydroxytetradecanoic acid, which was slurried with methyl tert-butyl ether (50ml) and was calculated to give a yield of 87%.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIG. 1-2.
As can be seen from fig. 1:1h NMR (400MHz, CDCl3) δ 15.28(s,1H), 3.08-3.03 (m,2H), 1.75-1.66 (m,10H),1.27(d, J ═ 14.3Hz,14H),1.16(d, J ═ 6.5Hz,4H), where chemical shift 7.26 is a deuterated chloroform solvent peak, hydrogen on carboxyl group with chemical shift around 11 is not shown, peak with chemical shift 0 is for calibration, negligible, chemical shifts 3.8 and 2.35 are impurity peaks, suspected of being an impurity intermediate with incomplete condensation or a raw material peak with incomplete reaction;
as can be seen from fig. 2: the molecular weight of the compound is 384.46, ES-looks for a hydrogen reduction peak 383.28.
(2) Preparation of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid by reduction of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid
The specific reaction process is as follows:
adding 15g (39mmol) of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid into a reaction bottle under the protection of nitrogen, adding dichloromethane, stirring for dissolving, cooling to 2-0 ℃, adding 23.6g (390mmol) of acetic acid, stirring, adding 4.4g (117mmol) of sodium borohydride, continuing to react for 2-3 h, extracting the reaction solution twice by using saturated sodium bicarbonate (150ml), washing once by using purified water (150ml), washing by using saturated saline water (150ml), and drying an organic phase by using anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid; the crude product was slurried with methyl tert-butyl ether (35ml) to give the product in 46% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively; wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 3 to 4.
As can be seen from fig. 3:1h NMR (400MHz, CDCl3) δ 3.49(t, J ═ 5.0Hz,1H),2.16 to 2.04(m,2H),1.75(dd, J ═ 18.9,8.4Hz,8H),1.44(dd, J ═ 10.2,5.7Hz,2H),1.33 to 1.17(m,20H), where chemical shift 7.26 is a deuterated chloroform solvent peak, chemical shift 0 is a peak for calibration, negligible, chemical shift 11 is not shown for hydrogen on the carboxyl group, chemical shift 15.3 is a peak for hydrogen on the enol bond on the incompletely reduced raw material, chemical shifts 3.1 and 3.8 are impurity peaks, suspected of incompletely reduced impurity intermediates or incompletely reduced raw material peaks;
as can be seen from fig. 4: the molecular weight of the compound is 370.48, ES-looks for a hydrogen reduction peak 369.26.
Example 3
Tetradecyl diacid is used as a raw material to prepare a tetradecyl acid derivative:
(1) condensation of tetradecyl diacid and isopropylidene malonate to prepare 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid
The specific reaction process is as follows:
under the protection of nitrogen, respectively adding 20g (77mmol) of tetradecyl diacid, 11.7g (81mmol) of isopropylidene malonate and 400ml of dichloromethane into a reaction bottle, stirring, cooling to-2 to-6 ℃, adding 18.8g (153.8mmol) of 4-dimethylamino pyridine, reacting for 8 to 12min, then adding 12.5g (99mmol) of N, N' -diisopropyl carbodiimide, moving to room temperature, reacting for 12h, extracting the post-treatment with 10% citric acid aqueous solution (200ml) twice, washing with purified water (200ml) once, washing with saturated saline water (200ml), and drying the organic phase with anhydrous sodium sulfate (20 g); the solvent was removed by rotary evaporation to give crude 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxan-5-enyl) -14-hydroxytetradecanoic acid, which was slurried with methyl tert-butyl ether (50ml) and was calculated to give a yield of 87%.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIG. 1-2.
As can be seen from fig. 1:1h NMR (400MHz, CDCl3) δ 15.28(s,1H), 3.08-3.03 (m,2H), 1.75-1.66 (m,10H),1.27(d, J ═ 14.3Hz,14H),1.16(d, J ═ 6.5Hz,4H), where chemical shift 7.26 is a deuterated chloroform solvent peak, hydrogen on carboxyl group with chemical shift around 11 is not shown, peak with chemical shift 0 is for calibration, negligible, chemical shifts 3.8 and 2.35 are impurity peaks, suspected of being an impurity intermediate with incomplete condensation or a raw material peak with incomplete reaction;
as can be seen from fig. 2: the molecular weight of the compound is 384.46, ES-looks for a hydrogen reduction peak 383.28.
(2) Preparation of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid by reduction of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid
The specific reaction process is as follows:
adding 15g (39mmol) of 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -14-hydroxytetradecanoic acid into a round-bottom flask under the protection of nitrogen, adding dichloromethane, stirring for dissolving, cooling to 2-0 ℃, adding 34.9g (576.8mol) of acetic acid, stirring, adding 7.17g (189.5mmol) of sodium borohydride, continuing to react for 2-3 h, extracting the reaction solution twice by using saturated sodium bicarbonate (150ml), washing once by using purified water (150ml), washing by using saturated saline (150ml), and drying an organic phase by using anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 14- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) tetradecanoic acid; the crude product was slurried with methyl tert-butyl ether (35ml) to give the product in 46% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively; wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 3 to 4.
As can be seen from fig. 3:1h NMR (400MHz, CDCl3) δ 3.49(t, J ═ 5.0Hz,1H),2.16 to 2.04(m,2H),1.75(dd, J ═ 18.9,8.4Hz,8H),1.44(dd, J ═ 10.2,5.7Hz,2H),1.33 to 1.17(m,20H), where chemical shift 7.26 is a deuterated chloroform solvent peak, chemical shift 0 is a peak for calibration, negligible, chemical shift 11 is not shown for hydrogen on the carboxyl group, chemical shift 15.3 is a peak for hydrogen on the enol bond on the incompletely reduced raw material, chemical shifts 3.1 and 3.8 are impurity peaks, suspected of incompletely reduced impurity intermediates or incompletely reduced raw material peaks;
as can be seen from fig. 4: the molecular weight of the compound is 370.48, ES-looks for a hydrogen reduction peak 369.26.
Example 4
Preparing hexadecanoic acid derivatives by using hexadecyl diacid as a raw material:
(1) condensation of hexadecyl diacid and isopropylidene malonate to prepare 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid
The specific reaction process is as follows:
under the protection of nitrogen, adding 20g (69.8mmol) of hexadecyl diacid and 10g (69.8mmol) of propylene malonate into a reaction bottle, adding dichloromethane (400ml), stirring, cooling to-2-6 ℃, adding 8.6g (70.4mmol) of 4-dimethylamino pyridine, reacting for 8-12 min, adding 8.9g (70.5mmol) of N, N' -diisopropylcarbodiimide, moving to room temperature, reacting for 12h, extracting the post-treatment with 10% citric acid aqueous solution (200ml) twice, washing with purified water (200ml) once, washing with saturated saline water (200ml), and drying the organic phase with anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid; the crude product was slurried with methyl tert-butyl ether (50ml) to give the product in 79% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 5 to 6.
As can be seen from fig. 5:1h NMR (400MHz, CDCl3) δ 15.29(s,1H),3.83(dt, J ═ 12.8,6.4Hz,2H),3.11 to 3.01(m,2H),1.75 to 1.67(m,8H),1.37 to 1.04(m,22H), where chemical shift 7.26 is a deuterated chloroform solvent peak, no hydrogen is shown on the carboxyl group at chemical shift around 11, and a peak at chemical shift 0 is used for calibration;
as can be seen from fig. 6: the molecular weight of the compound is 412.52, ES-looks for a hydrogen reduction peak 411.27.
(2) Preparation of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid by reduction of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) hexadecanoic acid
The specific reaction process is as follows:
adding 15g (36.4mmol) of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid into a reaction bottle under the protection of nitrogen, adding dichloromethane, stirring for dissolving, cooling to 2-0 ℃, adding 17.6g (290mmol) of acetic acid, stirring, adding 1.5g (39.6mmol) of sodium borohydride, continuing to react for 2-3 h, extracting the reaction solution twice by using saturated sodium bicarbonate (150ml), washing once by using purified water (150ml), washing by using saturated saline (150ml), and drying by using anhydrous sodium sulfate (20g) for an organic phase; removing the solvent by rotary evaporation to obtain crude 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) hexadecanoic acid; the crude product was slurried with methyl tert-butyl ether (35ml) to give the product in 40% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 7 to 8.
As can be seen from fig. 7:1h NMR (400MHz, CDCl3) δ 3.56-3.40 (m,1H), 2.12-2.01 (m,2H), 1.82-1.54 (m,10H), 1.51-1.34 (m,4H),1.21(s,20H), where chemical shift 7.26 is a deuterated chloroform solvent peak, hydrogen on carboxyl group with chemical shift around 11 is not shown, peak with chemical shift 0 is for calibration, peak with chemical shift 15.29 is hydrogen on enol bond on raw material that is not completely reduced, chemical shifts 3.1 and 5.3 are impurity peaks, suspected of being an impurity intermediate that is not completely condensed or a raw material that is not completely reacted;
as can be seen from fig. 8: the molecular weight of the compound is 398.53, and ES-looks for a hydrogen reduction peak 397.31.
Example 5
Preparing hexadecanoic acid derivatives by using hexadecyl diacid as a raw material:
(1) condensation of hexadecyl diacid and isopropylidene malonate to prepare 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid
The specific reaction process is as follows:
under the protection of nitrogen, adding 20g (69.8mmol) of hexadecyl diacid and 11g (76.8mmol) of isopropylidene malonate into a reaction bottle, adding 400ml of dichloromethane, stirring, cooling to-2-6 ℃, adding 12.7g (104mmol) of 4-dimethylaminopyridine, reacting for 8-12 min, adding 9.6g (76.8mmol) of N, N' -diisopropylcarbodiimide, moving to room temperature for reaction for 12h, extracting the post-treatment with 10% citric acid aqueous solution (200ml) twice, washing once with purified water (200ml), washing with saturated saline water (200ml), and drying an organic phase with anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid; the crude product was slurried with methyl tert-butyl ether (50ml) to give the product in 80% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 5 to 6.
As can be seen from fig. 5:1h NMR (400MHz, CDCl3) δ 15.29(s,1H),3.83(dt, J ═ 12.8,6.4Hz,2H),3.11 to 3.01(m,2H),1.75 to 1.67(m,8H),1.37 to 1.04(m,22H), where chemical shift 7.26 is a deuterated chloroform solvent peak, no hydrogen is shown on the carboxyl group at chemical shift around 11, and a peak at chemical shift 0 is used for calibration;
as can be seen from fig. 6: the molecular weight of the compound is 412.52, ES-looks for a hydrogen reduction peak 411.27.
(2) Preparation of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid by reduction of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) hexadecanoic acid
The specific reaction process is as follows:
adding 15g (36.4mmol) of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid into a reaction bottle under the protection of nitrogen, adding dichloromethane, stirring for dissolving, cooling to 2-0 ℃, adding 22g (364mmol) of acetic acid, stirring, adding 4.1g (109mmol) of sodium borohydride, continuing to react for 2-3 h, extracting the reaction solution twice by using saturated sodium bicarbonate (150ml), washing once by using purified water (150ml), washing by using saturated saline water (150ml), and drying an organic phase by using anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) hexadecanoic acid; the crude product was slurried with methyl tert-butyl ether (35ml) to give the product in 40% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 7 to 8.
As can be seen from fig. 7:1h NMR (400MHz, CDCl3) δ 3.56-3.40 (m,1H), 2.12-2.01 (m,2H), 1.82-1.54 (m,10H), 1.51-1.34 (m,4H),1.21(s,20H), where chemical shift 7.26 is a deuterated chloroform solvent peak, hydrogen on carboxyl group with chemical shift around 11 is not shown, peak with chemical shift 0 is for calibration, peak with chemical shift 15.29 is hydrogen on enol bond on raw material that is not completely reduced, chemical shifts 3.1 and 5.3 are impurity peaks, suspected of being an impurity intermediate that is not completely condensed or a raw material that is not completely reacted;
as can be seen from fig. 8: the molecular weight of the compound is 398.53, and ES-looks for a hydrogen reduction peak 397.31.
Example 6
Preparing hexadecanoic acid derivatives by using hexadecyl diacid as a raw material:
(1) condensation of hexadecyl diacid and isopropylidene malonate to prepare 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid
The specific reaction process is as follows:
under the protection of nitrogen, adding 20g (69.8mmol) of hexadecyl diacid and 13.1g (90.7mmol) of isopropylidene malonate into a reaction bottle, adding 400ml of dichloromethane, stirring, cooling to-2-6 ℃, adding 17g (139mmol) of 4-dimethylaminopyridine, reacting for 8-12 min, adding 11.4g (90.7mmol) of N, N' -diisopropylcarbodiimide, moving to room temperature for reaction for 12h, extracting the post-treatment with 10% citric acid aqueous solution (200ml) twice, washing once with purified water (200ml), washing with saturated saline water (200ml), and drying an organic phase with anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid; pulping the crude product with methyl tert-butyl ether (50ml) to obtain product with yield of 80%, and subjecting the prepared product to nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 5 to 6.
As can be seen from fig. 5:1H NMR(400MHz,CDCl3)δ15.29(s,1H) 3.83(dt, J ═ 12.8,6.4Hz,2H),3.11 to 3.01(m,2H),1.75 to 1.67(m,8H),1.37 to 1.04(m,22H), where chemical shift 7.26 is the deuterated chloroform solvent peak, no hydrogen is shown on the carboxyl group at chemical shift around 11, and the peak at chemical shift 0 is negligible for calibration;
as can be seen from fig. 6: the molecular weight of the compound is 412.52, ES-looks for a hydrogen reduction peak 411.27.
(2) Preparation of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid by reduction of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) hexadecanoic acid
The specific reaction process is as follows:
adding 15g (36mmol) of 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-alkenyl) -16-hydroxyhexadecanoic acid into a round-bottom flask under the protection of nitrogen, adding dichloromethane, stirring for dissolving, cooling to 2-0 ℃, adding 32.5g (537mmol) of acetic acid, stirring, adding 6.8g (179mmol) of sodium borohydride, continuing to react for 2-3 h, extracting the reaction solution twice by using saturated sodium bicarbonate (150ml), washing once by using purified water (150ml), washing by using saturated saline water (150ml), and drying an organic phase by using anhydrous sodium sulfate (20 g); removing the solvent by rotary evaporation to obtain crude 16- (2, 2-dimethyl-4, 6-dioxy-1, 3-dioxanyl-5-) hexadecanoic acid; the crude product was slurried with methyl tert-butyl ether (35ml) to give the product in 40% yield.
Taking the prepared product to perform nuclear magnetic resonance and mass spectrometry respectively, wherein1The H NMR spectrum and the mass spectrum are shown in FIGS. 7 to 8.
As can be seen from fig. 7:1h NMR (400MHz, CDCl3) delta 3.56-3.40 (m,1H), 2.12-2.01 (m,2H), 1.82-1.54 (m,10H), 1.51-1.34 (m,4H),1.21(s,20H), where chemical shift 7.26 is a deuterated chloroform solvent peak, no hydrogen is shown on the carboxyl group with chemical shift around 11, a peak with chemical shift 0 is for calibration, a peak with chemical shift 15.29 is hydrogen on the enol bond on the starting material which is not completely reduced, chemical shifts 3.1 and 5.3 are for calibrationAn impurity peak suspected of being an impurity intermediate that is not completely condensed or a raw material peak that is not completely reacted;
as can be seen from fig. 8: the molecular weight of the compound is 398.53, and ES-looks for a hydrogen reduction peak 397.31.
When the long-chain alkanoic acid derivative is prepared by the method, the larger the value of n is, the easier the reaction is theoretically realized.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (13)
1. A long-chain alkanoic acid derivative has a structure shown in formula D
Wherein n is an integer of 0 or more.
2. A process for the preparation of a long-chain alkanoic acid derivative according to claim 1, comprising the steps of:
reacting the long-chain hydroxy alkanoic acid derivative shown as E in the presence of sodium borohydride to prepare a long-chain alkanoic acid derivative shown as D, wherein in the following equation, n is an integer greater than or equal to 0;
3. the method for producing a long-chain alkanoic acid derivative according to claim 2, wherein the step of reacting E to D is as follows:
and E, adding dichloromethane for dissolving, cooling to-5 ℃, adding acetic acid for stirring, adding sodium borohydride for reacting for 1-2 hours, extracting twice with a saturated sodium bicarbonate solution, washing with purified water, then with saturated salt solution, drying with anhydrous sodium sulfate, and pulping with methyl tert-butyl ether as a solvent to obtain D.
4. The method for preparing a long-chain alkanoic acid derivative according to claim 3, wherein in the step of preparing D from E, the molar ratio of E to acetic acid is 1: 8-15.
5. The method for preparing a long-chain alkanoic acid derivative according to claim 3, wherein in the step of preparing D from E, the molar ratio of E to sodium borohydride is 1: 1 to 5.
6. The method for producing a long-chain alkanoic acid derivative according to claim 2, further comprising the steps of:
condensing the long-chain alkyl diacid and isopropylidene malonate as shown in B' to prepare a substance shown in E, wherein n is an integer which is more than or equal to 0 in the following equation;
7. the method for preparing a long-chain alkanoic acid derivative according to claim 6, wherein the step of preparing C by reacting A' with F comprises:
and mixing A 'and F, adding dichloromethane for dissolving, cooling to-10-0 ℃ under the protection of inert gas, sequentially adding a catalyst 4-dimethylaminopyridine and a condensing agent N, N' -diisopropylcarbodiimide, reacting for 8-16 hours, extracting twice with a citric acid aqueous solution, washing with purified water, washing with saturated salt water, drying with anhydrous sodium sulfate, and pulping with methyl tert-butyl ether as a solvent to obtain E.
8. The method for preparing a long-chain alkanoic acid derivative according to claim 7, wherein in the step of preparing C by reacting A 'with F, the molar ratio of A' to F is 1: 1 to 1.3.
9. The method according to claim 7, wherein in the step of reacting A ' with F to obtain C, the molar ratio of A ' to N, N ' -diisopropylcarbodiimide is 1: 1 to 1.3.
10. The method of claim 7, wherein in the step of reacting a 'with F to produce C, the molar ratio of a' to 4-dimethylaminopyridine is 1: 1 to 2.
11. The long-chain alkanoic acid derivative according to claim 1, 2 or 6, wherein n is an integer of 6 or more.
12. The long-chain alkanoic acid derivative as claimed in claim 11, wherein n-6 or n-7.
13. The long-chain alkanoic acid derivative according to claim 1, wherein said long-chain alkanoic acid derivative is used for medical synthesis.
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| EVELINE HAULOTTE等: "Biosynthesis of Defensive Coccinellidae Alkaloids: Incorporation of Fatty Acids in Adaline, Coccinelline, and Harmonine", 《EUR. J. ORG. CHEM.》 * |
| JUDY OBAZA等: "A Malonic Ester Synthesis with Acid Chlorides. The Homologation of Oioic Acids", 《SYNTHETIC COMMUNICATIONS》 * |
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