CN102321112A - Synthesis method for 5-silica-alpha-ketone carbonyl isoheptanoate, 6-silica-alpha-ketone carbonyl isooctanoate and esters thereof - Google Patents
Synthesis method for 5-silica-alpha-ketone carbonyl isoheptanoate, 6-silica-alpha-ketone carbonyl isooctanoate and esters thereof Download PDFInfo
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- CN102321112A CN102321112A CN201110138416A CN201110138416A CN102321112A CN 102321112 A CN102321112 A CN 102321112A CN 201110138416 A CN201110138416 A CN 201110138416A CN 201110138416 A CN201110138416 A CN 201110138416A CN 102321112 A CN102321112 A CN 102321112A
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- NBNMPZBABUHOSG-UHFFFAOYSA-N CC(C)(CCCC(O)=O)N=O Chemical compound CC(C)(CCCC(O)=O)N=O NBNMPZBABUHOSG-UHFFFAOYSA-N 0.000 description 1
- MSAPLXSDFFFJOV-UHFFFAOYSA-N CCOC(C1(O)OC(C)(C)CCC1)=O Chemical compound CCOC(C1(O)OC(C)(C)CCC1)=O MSAPLXSDFFFJOV-UHFFFAOYSA-N 0.000 description 1
- FQTIYMRSUOADDK-UHFFFAOYSA-N CCOC(CCBr)=O Chemical compound CCOC(CCBr)=O FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention relates to a synthesis method for 5-silica-alpha-ketone carbonyl isoheptanoate, 6-silica-alpha-ketone carbonyl isooctanoate and esters thereof. The compounds comprise the compounds with the following general formulas 1 and 2, wherein R1 is independently silica trimethyl, silica triethyl, silica isopropylated phenyl, silica phenyl methyl diphenyl, silica diisopropyl pheny, silica triphenyl, silica dimethyl tertbutyl, silica dimethyl phenyl, silica diphenyl tertiary butyl and the like, and R2 is independently H, C1 to 20 linear chain or branch chain alkyl, phenyl, substituted alkyl, substituted phenyl, benzyl, substituted benzyl and the like. The compounds modified in such a way and derivatives of the compounds have the advantages that one functional group is added, and wide purposes can be realized in the organic synthesis.
Description
Technical field
The present invention relates to a kind of 5-siloxy-α-ketone carbonyl isoamyl acetic acid and 6-siloxy-α-ketone carbonyl isocaprylic acid and ester class and compound method.
Background technology
Alpha-ketoacid is one type of bifunctional compound, in organic synthesis and biological processes, plays the reactive intermediate effect of presenting under opening.Like conduct fat, carbohydrate, ribose, porphyrin, amino acid and proteinic synthetic intermediate (J.Acc.Chem.Res.1974,40; Bioorg.Chem.1985,13,335).Alpha-ketoacid is synthetic various enzyme inhibitorss and alkaloidal important intermediate.Be applied to the synthetic of multiple compounds such as vasotonia attitude transferase inhibitor, serpin, NSC 142196, high NSC 142196; And these compounds have certain curative effect (SCI to the treatment of hypertension, cancer etc. respectively; 1983; 4,389; Org.Prep.Proced.Int.1989,21,501).In addition, considerable alpha-ketoacid ester such as pyruvate smell fragrance, natural being present in the leavened food such as drinks (J.Sci.Food.Agric.1979,30,319), thereby can cook foodstuff additive.
Because the alpha-ketoacid ester is increasingly extensive in biology, medicine, agricultural chemicals, spices and Applications in Food Industry, its synthetic people's attention that always receives.Many chemists are effectively synthesizing of alpha-ketoacid to have done conscientious careful research work (Recueil des Travaux Chimiques des Pays-Bas, 1993,112,471).
Summary of the invention
The object of the present invention is to provide a kind of 5-siloxy-α-ketone carbonyl isoamyl acetic acid and 6-siloxy-α-ketone carbonyl isocaprylic acid and ester class and compound method.Compound and verivate thereof through modifying have like this increased a functional group, in organic synthesis, have extensive use, are used for biology, medicine, agricultural chemicals, spices and foodstuffs industry.
5-siloxy-α provided by the invention-ketone carbonyl isoamyl acetic acid and 6-siloxy-α-ketone carbonyl isocaprylic acid and ester compound thereof are the compounds with following general formula 1 and 2:
R wherein
1Be independently trimethyl silicon based, triethyl is silica-based, triisopropylsilyl, the methyldiphenyl base is silica-based, diisopropyl phenyl is silica-based, triphenyl is silica-based, the dimethyl-tertiary butyl is silica-based, 3,5-dimethylphenyl is silica-based, the phenylbenzene tertiary butyl is silica-based etc.R
2Be H independently, C
1～20The alkyl of straight chain or side chain, phenyl, substituted alkyl, substituted-phenyl, benzyl, substituted benzyl etc.
Compound of the present invention, its optional structure is:
Compound 1 provided by the invention and 2 synthesis step are:
R
1, R
2Like above-mentioned definition; Concrete steps:
1) compound 8 in-50 ℃ to 100 ℃ scope, obtains compound 9 with the reaction of methyl Grignard reagent in inert organic solvents, and products therefrom carries out purifying through underpressure distillation.Compound 8 is 1 with the mol ratio of methyl Grignard reagent reaction: 1-3.Said inert solvent is an ethers reagent, is preferably ether, THF etc.
2) compound 9 in-50 ℃ to 50 ℃ scope, under the effect of alkali, with the silica reagent reaction, obtains compound 10 in inert organic solvents, and products therefrom carries out purifying through underpressure distillation.Said alkali can be organic or inorganic alkali, is preferably pyridine, triethylamine etc.; Said inert solvent is methylene dichloride, ether, THF, ETHYLE ACETATE, toluene, acetonitrile etc.; Said silica reagent is preferably trimethylchlorosilane, trifluoromethanesulfonic acid trimethylsilyl group, chlorotriethyl silane, tri isopropyl chlorosilane, methyldiphenyl base chlorosilane, diisopropyl phenyl chlorosilane, tri-phenyl chloride, dimethyl-tertiary butyl chloride silane, 3,5-dimethylphenyl chlorosilane, phenylbenzene tertiary butyl chloride silane, trifluoromethanesulfonic acid dimethyl-tertiary butyl estersil etc.
3) compound 10 in-80 ℃ to 50 ℃ scope, is prepared into Grignard reagent in inert solvent, with the oxalate diester reaction, obtains compound 1 again, and products therefrom carries out purifying through underpressure distillation.Said inert solvent is an ethers reagent, is preferably ether, THF etc.Oxalate diester is alkyl or aryl ester, is preferably oxalic acid diethyl ester.
4) compound 11 in-50 ℃ to 50 ℃ scope, is reduced the agent reduction and obtains compound 12 in inert solvent, and products therefrom carries out purifying through distillation.Said inert solvent is an ethers reagent, is preferably ether, THF etc.; Said reductive agent is preferably Lithium Aluminium Hydride.
5) compound 12 and hydrobromic concentrated sulfuric acid solution reflux obtain compound 13, and products therefrom carries out purifying through distillation.
6) compound 13 in-80 ℃ to 50 ℃ scope, is prepared into Grignard reagent in inert solvent, with the oxalate diester reaction, obtains compound 14 again, and products therefrom carries out purifying through underpressure distillation.Said inert solvent is an ethers reagent, is preferably ether, THF etc.Oxalate diester is alkyl or aryl ester, is preferably oxalic acid diethyl ester.
7) compound 14 is in inert solvent, and in buffered soln, oxidized dose of oxidation obtains compound 15, and products therefrom carries out purifying through underpressure distillation.The ratio that described inert solvent is preferably acetonitrile and water is 3: 2 a mixed solvent; Said alkali is preferably sodium hydrogencarbonate; Said oxygenant is preferably potassium hydrogen persulfate mixture (2KHSO
5KHSO
4K
2SO
4); Said buffered soln is preferably disodium EDTA.
8) compound 15 under the catalysis of alkali, with the scope internal reaction of silica reagent at 0 ℃ to 100 ℃, obtains compound 16 in inert solvent, and products therefrom carries out purifying through underpressure distillation.Said inert solvent is ethers, ester class, halohydrocarbon etc., is preferably methylene dichloride, 1,2-ethylene dichloride, trichloromethane etc.; Said alkali is organic or inorganic alkali, is preferably triethylamine, pyridine, N, N-diisopropylethylamine, 4-Dimethylamino pyridine etc.; Said silica reagent is preferably trimethylchlorosilane, trifluoromethanesulfonic acid trimethylsilyl group, chlorotriethyl silane, tri isopropyl chlorosilane, methyldiphenyl base chlorosilane, diisopropyl phenyl chlorosilane, tri-phenyl chloride, dimethyl-tertiary butyl chloride silane, 3,5-dimethylphenyl chlorosilane, phenylbenzene tertiary butyl chloride silane, trifluoromethanesulfonic acid dimethyl-tertiary butyl estersil etc.
9) compound 16 under acid catalysis, with the fluorine reagent reaction, obtains compound 2 in inert solvent.Said inert solvent is preferably acetonitrile; Said acid is preferably acetate; Said fluorine reagent is preferably Potassium monofluoride, cesium fluoride, triethylamine trihydrofluoride (Et
3N3HF), trifluoroacetic acid, hydrogen fluoride, boron trifluoride, tetrabutyl ammonium fluoride etc.
The invention provides a kind of 5-siloxy-α-ketone carbonyl isoamyl acetic acid and 6-siloxy-α-ketone carbonyl isocaprylic acid and ester class and compound method.Compound and verivate thereof through modifying have like this increased a functional group, in organic synthesis, will have extensive use, are used for biology, medicine, agricultural chemicals, spices and foodstuffs industry.
Embodiment
Below through the embodiment of embodiment form foregoing of the present invention is done further to specify again.But should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment, all technology that realizes based on foregoing of the present invention all belong to scope of the present invention.Yield of the present invention is without optimization.
The preparation of embodiment 14-bromo-2-methyl-2-butanols (compound 9)
(18.1g drips MeMgI (220mmol) solution for preparing in diethyl ether solution 100mmol), add continued reaction 0.5h, adds 2M hydrochloric acid and is adjusted to slightly acidic, and extracted with diethyl ether merges organic phase, uses saturated NaHCO successively to three ethyl bromides 8
3Solution, saturated common salt water washing, anhydrous Na
2SO
4Drying, revolve desolvate thick product.Underpressure distillation gets colourless oil liquid 8.4g, yield 50%.
1H NMR (400MHz, CDCl
3): δ 3.48 (t, J=8Hz, 2H), 2.07 (t, J=8Hz, 2H), 1.24 (s, 6H).
The preparation of embodiment 24-bromo-2-methyl-silica-based butyl ether of the 2-dimethyl-tertiary butyl (compound 17)
With trifluoromethanesulfonic acid dimethyl-tertiary butyl estersil (11.5mL, 50mmol) join bromhydrin (6.63g, 40mmol) and pyridine (9mL in methylene dichloride 100mmol) (100mL) solution, adds saturated NaHCO behind the reaction 1h
3Solution, separatory, extracted with diethyl ether merges organic phase, uses saturated NaHCO successively
3Solution, saturated common salt water washing, anhydrous anhydrous Na
2SO
4Drying, revolve desolvate thick product.Underpressure distillation gets 6.96g colorless oil compound 17, yield 65%.
1H NMR (400MHz, CDCl
3): δ 3.46 (t, J=8Hz, 2H), 2.02 (t, J=8Hz, 2H), 1.21 (s, 6H), 0.84 (s, 9H), 0.06 (s, 6H). (the TBS=dimethyl-tertiary butyl is silica-based).
The preparation of embodiment 35-methyl-5-dimethyl-tertiary butyl siloxy-2-oxygen-NSC 8882 (compound 3)
Under-78 ℃, (30mmol 1M) is added drop-wise to ethyl oxalate (3.65g with the THF solution of the Grignard reagent for preparing; In the THF solution of 30mL 25mmol), add the continued stirring reaction, remove cryostat; Drip the 1M hydrochloric acid soln to slightly acidic, separatory, extracted with diethyl ether; Merge organic phase, use saturated NaHCO successively
3Solution, saturated common salt water washing, anhydrous Na
2SO
4Drying, revolve desolvate thick product.Underpressure distillation gets colorless oil compound 3.6g, yield 62%.
1H NMR (400MHz, CDCl
3) δ 4.26 (s, J=7.2Hz, 2H), 2.90 (t, J=8.0Hz, 2H), 1.69 (t, J=8Hz, 2H), 1.31 (t, J=6.4Hz, 3H), 1.18 (s, 6H), 0.80 (s, 9H), 0.02 (s, 6H).
The preparation of embodiment 45-methyl-5-dimethyl-tertiary butyl siloxy-2-oxygen-caproic acid (compound 4)
Under the ice bath, (604mg 2mmol) is dissolved in the 2mL methyl alcohol, splashes in the 2mL 2M NaOH solution, continues stirring reaction, adds 0.1M HCl solution and transfers pH to 3-4, and extracted with diethyl ether merges organic phase, saturated common salt washing, anhydrous Na with compound 3
2SO
4Drying, revolve desolvate 0.53g compound 4, yield 97%.
1H?NMR(400MHz，CDCl
3)：δ8.01(s，1H)，3.02(t，J＝7.6Hz，2H)，1.76(t，J＝7.6Hz，2H)，1.22(s，6H)，0.82(s，9H)，0.05(s，6H).
The preparation of embodiment 5 isohexyl alcohols (compound 12)
(58g, 250ml diethyl ether solution 0.5mol) slowly is added drop-wise to LiAlH with isocaproic acid 11
4(20.9g in 500mL anhydrous diethyl ether 0.55mol), adds the back and continues stirring reaction under the room temperature, adds the water aftertreatment and gets crude product and drain the back underpressure distillation and obtain compound 12, receives the 48g product, yield 95%.
1H?NMR(400MHz，CDCl
3)δ3.61(t，J＝6.4Hz，2H)，1.55(m，3H)，1.18-1.24(m，2H)，0.87(d，J＝6.4Hz，6H).
The preparation of embodiment 6 bromo isohexanes (compound 3)
(213g, 1.25mol) (30.69g 0.55mol), adds (52g, 0.5mol) isohexyl alcohol to the middle adding vitriol oil then to 48% Hydrogen bromide.Heat slow backflow 6-8h. cooling, separatory, petroleum ether extraction water three times merges organic phase, with small amount of cold vitriol oil washing organic phase, uses zero(ppm) water, saturated sodium bicarbonate, saturated common salt water washing after drying more successively, revolves to desolventize.Air distillation gets colourless transparent liquid 61.87g (b.p.146 ℃), yield 75%.
1H NMR (400MHz, CDCl
3) δ 3.39 (t, J=6.8Hz, 2H), 1.82-1.89 (m, 2H), 1.52-1.60 (m, 1H), 1.27-1.33 (m, 2H), 0.90 (d, J=6.8Hz, 6H).
The preparation of embodiment 76-methyl-2-oxygen-oil of cognac (compound 18)
Under-80 ℃, with bromo isohexane 13 (82.5g, 0.5mol) concentration of preparation is that the ether Grignard reagent of 1M is added drop-wise to ethyl oxalate (73g; 0.5mol) the 500mL anhydrous diethyl ether in, add the continued stirring reaction, then Dropwise 5 00mL 2MHCl; Be hydrolyzed into the solution clarification, separatory, water layer are with extracted with diethyl ether for several times; Merge organic phase, use saturated NaHCO successively
3The saturated NaCl solution washing of solution, anhydrous magnesium sulfate drying filters, and steaming desolventizes, and underpressure distillation then gets light yellow transparent liquid 82g, yield 89%.
1H NMR (400MHz, CDCl
3) δ 4.31 (q, J=6.4Hz, 2H), 2.80 (t, J=6.4Hz, 2H), 1.50-1.66 (m, 3H), 1.36 (t, J=6.4Hz, 3H), 1.17 (m, 2H), 0.83 (d, J=6.4Hz, 6H).
The preparation of embodiment 8 compounds 15
Under the room temperature, (10.42g is 28mmol) with 672mL CH to ketone ester 18 is housed
3CN and 448mL 0.4mM Na
2EDTA solution adds 34.4g potassium hydrogen persulfate mixture (2KHSO
5KHSO
4K
28O
4, 56mmol) and NaHCO
3(11.3g48mmol) mixture after having reacted, revolves CH
3CN, water is used Na
2SO
4Saturated, repeatedly use ethyl acetate extraction, merge organic phase, use saturated NaHCO
3Wash twice, with the saturated common salt washing once, use anhydrous Na again
2SO
4Drying is revolved dried thick product, and underpressure distillation gets 3.5g compound 19 then, yield 31%.
1H NMR (400MHz, CDCl
3) δ 4.20-4.25 (m, 2H), 3.56 (s, 1H, OH), 1.92-2.01 (m, 2H), 1.52-1.73 (m, 4H), 1.38 (s, 3H), 1.30 (t, J=7.2Hz, 3H), 1.18 (s, 3H).
The preparation of embodiment 9 compounds 5
To be equipped with compound 19 (202mg, add successively in 8mL dichloromethane solution 1mmol) pyridine (0.17mL, 2mmol) and trimethylchlorosilane (0.15mL, 1.2mmol).After having reacted, add the saturated NaHCO of about 10mL
3Solution, stirring reaction, water merges organic phase 3 times with extracted with diethyl ether, successively with zero(ppm) water, saturated common salt washing, anhydrous sodium sulfate drying.Revolve dry chromatography and get 134mg compound 5, yield 49%.(TMS=is trimethyl silicon based).
1H?NMR(400MHz，CDCl
3)δ4.31(q，J＝6.4Hz，2H)，2.85(t，J＝6.4Hz，2H)，1.66-1.74(m，2H)，1.42-1.46(m，2H)，1.37(t，J＝7.2Hz，3H)，1.22(s，6H)，0.10(s，9H).
The preparation of embodiment 10 compounds 20
Reflux down, to compound 19 (3.85g, ClCH 19mmol) are housed
2CH
2Cl 100mL solution adds pyridine successively, and (4.6mL, 57mmol) (10.9mL 47mmol), after having reacted, is cooled to room temperature, adds the saturated NaHCO of 100mL with trifluoromethanesulfonic acid dimethyl-tertiary butyl estersil
3Solution, separatory, water is used extracted with diethyl ether, merges organic phase, uses saturated NaHCO successively
3Solution, saturated common salt washing, anhydrous Na
2SO
4Drying is revolved dried crude product, and underpressure distillation gets 6.5g colorless oil 20 then, yield 80%.
1H?NMR(400MHz，CDCl
3)δ6.00(t，J＝7.2Hz，1H)，4.18(q，J＝7.2Hz，2H)，2.25-2.30(m，2H)，1.49-1.53(m.2H)，1.30(t，J＝7.2Hz，3H)，1.21(s，6H)，0.97(s，9H)，0.85(s，9H)，0.16(s，6H)，0.07(s，6H).
The preparation of embodiment 11 compounds 6
Under the room temperature, compound 20 (6.45g, 15mmol), cesium fluoride (4.56g, 30mmol) and acetate (3.8mL, 75mmol), stirring at room reaction in the 50mL acetonitrile after react, is dissolved in the 500mL ether, repeatedly washes saturated NaHCO afterwards
3Solution is washed till neutrality, saturated common salt washing, anhydrous Na
2SO
4Dry.Underpressure distillation gets 4.03g compound 6, yield 85%.
1H NMR (400MHz, CDCl
3) δ 4.30 (q, J=6.4Hz, 2H), 2.82 (t, J=6.4Hz, 2H), 1.68-1.75 (m, 2H), 1.40-1.44 (m, 2H), 1.36 (t, J=7.2Hz, 3H), 1.19 (s, 6H), 0.84 (s, 9H), 0.05 (s, 6H).
The preparation of embodiment 12 compounds 7
Under the ice bath, (732mg 2mmol) is dissolved in the 2mL methyl alcohol, splashes in the 2mL2MNaOH solution, continues to stir 10min, adds 0.1M HCl solution and transfers pH to 3-4, and extracted with diethyl ether merges organic phase, saturated common salt washing, anhydrous Na with ketone ester 6
2SO
4Drying is revolved dried 0.56g compound 7, yield 97%.
1H?NMR(400MHz，CDCl
3)δ2.92(t，J＝6.4Hz，2H)，1.72-1.76(m，2H)，1.40-1.45(m，2H)，1.20(s，6H)，0.84(s，9H)，0.05(s，6H)。
Claims (3)
1. 5-siloxy-α-ketone carbonyl isoamyl acetic acid and 6-siloxy-α-ketone carbonyl isocaprylic acid and ester compound thereof is characterized in that it has the compound of following general formula 1 and 2:
R wherein
1Be independently trimethyl silicon based, triethyl is silica-based, triisopropylsilyl, the methyldiphenyl base is silica-based, diisopropyl phenyl is silica-based, triphenyl is silica-based, the dimethyl-tertiary butyl is silica-based, 3,5-dimethylphenyl is silica-based, the phenylbenzene tertiary butyl is silica-based; R
2Be H independently, C
1～20Alkyl, aryl, substituted alkyl, substituted aryl.
2. according to the described compound of claim 1, it is characterized in that they are:
3. the compound method of the described compound of claim 1 is characterized in that the step of process is:
R
1, R
2Such as claim 1 definition; Concrete steps:
1) compound 8 in-50 ℃ to 100 ℃ scope, obtains compound 9 with the reaction of methyl Grignard reagent in inert organic solvents, and products therefrom carries out purifying through underpressure distillation; Compound 8 is 1 with the mol ratio of methyl Grignard reagent reaction: 1-3; Said inert solvent is ether, THF;
2) compound 9 in-50 ℃ to 50 ℃ scope, under the effect of alkali, with the silica reagent reaction, obtains compound 10 in inert organic solvents, and products therefrom carries out purifying through underpressure distillation; Said alkali is pyridine, triethylamine; Said inert solvent is methylene dichloride, ether, THF, ETHYLE ACETATE, toluene, acetonitrile; Said silica reagent is trimethylchlorosilane, trifluoromethanesulfonic acid trimethylsilyl group, chlorotriethyl silane, tri isopropyl chlorosilane, methyldiphenyl base chlorosilane, diisopropyl phenyl chlorosilane, tri-phenyl chloride, dimethyl-tertiary butyl chloride silane, 3,5-dimethylphenyl chlorosilane, phenylbenzene tertiary butyl chloride silane, trifluoromethanesulfonic acid dimethyl-tertiary butyl estersil;
3) compound 10 in-80 ℃ to 50 ℃ scope, is prepared into Grignard reagent in inert solvent, with the oxalate diester reaction, obtains compound 1 again, and products therefrom carries out purifying through underpressure distillation; Said inert solvent is ether, THF; Oxalate diester is an oxalic acid diethyl ester;
4) compound 11 in-50 ℃ to 50 ℃ scope, is reduced the agent reduction and obtains compound 12 in inert solvent, and products therefrom carries out purifying through distillation; Said inert solvent is ether, THF; Said reductive agent is a Lithium Aluminium Hydride;
5) compound 12 and hydrobromic concentrated sulfuric acid solution reflux obtain compound 13, and products therefrom carries out purifying through distillation;
6) compound 13 in-80 ℃ to 50 ℃ scope, is prepared into Grignard reagent in inert solvent, with the oxalate diester reaction, obtains compound 14 again, and products therefrom carries out purifying through underpressure distillation; Said inert solvent is ether, THF; Oxalate diester is an oxalic acid diethyl ester;
7) compound 14 is in inert solvent, and in disodium EDTA solution, oxidized dose of oxidation obtains compound 15, and products therefrom carries out purifying through underpressure distillation; The ratio that described inert solvent is preferably acetonitrile and water is 3: 2 a mixed solvent; Said alkali is preferably sodium hydrogencarbonate; Said oxygenant is potassium hydrogen persulfate mixture (Oxone, 2KHSO
5KHSO
4K
2SO
4);
8) compound 15 under the catalysis of alkali, with the scope internal reaction of silica reagent at 0 ℃ to 100 ℃, obtains compound 16 in inert solvent, and products therefrom carries out purifying through underpressure distillation; Said inert solvent is a methylene dichloride, 1,2-ethylene dichloride, trichloromethane; Said alkali is triethylamine, pyridine, N, N-diisopropylethylamine, 4-Dimethylamino pyridine; Said silica reagent is trimethylchlorosilane, trifluoromethanesulfonic acid trimethylsilyl group, chlorotriethyl silane, tri isopropyl chlorosilane, methyldiphenyl base chlorosilane, diisopropyl phenyl chlorosilane, tri-phenyl chloride, dimethyl-tertiary butyl chloride silane, 3,5-dimethylphenyl chlorosilane, phenylbenzene tertiary butyl chloride silane, trifluoromethanesulfonic acid dimethyl-tertiary butyl estersil;
9) compound 16 under acid catalysis, with the fluorine reagent reaction, obtains compound 2 in inert solvent; Said inert solvent is preferably acetonitrile; Said acid is preferably acetate; Said fluorination reagent is preferably Potassium monofluoride, cesium fluoride, triethylamine trihydrofluoride (Et
3N3HF), trifluoroacetic acid, hydrogen fluoride, boron trifluoride, tetrabutyl ammonium fluoride.
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| CN113735924A (en) * | 2021-09-01 | 2021-12-03 | 河北威远生物化工有限公司 | Preparation method of 23-ketone avermectin B2a/B2B derivative |
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| CN113735924A (en) * | 2021-09-01 | 2021-12-03 | 河北威远生物化工有限公司 | Preparation method of 23-ketone avermectin B2a/B2B derivative |
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