* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With sodium hydroxide In ethanol at 20℃; for 0.5 h;
The above crude 265K cyclization product (IV) and 400Kg of ethanol were withdrawn in a 1000 L reaction ax,Open mechanical agitation,One-time pumping has been equipped with a good solution of sodium hydroxide (40Kg sodium hydroxide dissolved in 195Kg water),Room temperature reaction 30 min (HPLC monitoring).After completion of the reaction, the ethanol was concentrated under reduced pressure.100Kg of water was poured into the concentrated ax, the aqueous phase was washed twice with 90Kg ethyl acetate, the aqueous phase was cooled to T? 10C, and concentrated hydrochloric acid was slowly added dropwise to pH = 3-4.The aqueous phase was extracted three times with 200 Kg of ethyl acetate. The organic phase was synthesized, washed with 200 Kg of saturated brine, dried over 30 Kg of anhydrous sodium sulfate, filtered and concentrated to give crude cyproterone.The crude ciprofibrate was decolored with 10 Kg of activated carbon,87 Kg of toluene and 275 Kg of n-hexane mixed solvent232Kg light yellow ciprofibric products (), the yield of 92percent, the total yield of 88percent.
91%
With sodium hydroxide In ethanol; water at 20℃; for 0.5 h; Large scale
The above 274Kg of the cyclized product crude and 500Kg of ethanol were pumped into a 1000L reaction ax and mechanical stirring was started. A good aqueous sodium hydroxide solution (41Kg sodium hydroxide dissolved in 200Kg water) was drawn in one time and reacted at room temperature for 30min monitor). After the reaction was completed, the ethanol was concentrated under reduced pressure. The concentrated ax was cooled to 10 ° C, concentrated hydrochloric acid was slowly dropped acidified to pH = 3-4. The aqueous phase was extracted three times with 200Kg of ethyl acetate, and the organic phase was synthesized, washed with 200Kg of saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated to obtain crude ciprofibrate. The crude ciprofibrate was decolorized with lOKg of activated carbon, and recrystallized from a mixed solvent of 200Kg of toluene and 200Kg of n-hexane to obtain 260Kg of light yellow ciprofibrate (V) in a yield of 91percent. The total yield86percent
With sodium hydroxide In methanol; water at 20℃; for 0.5 h;
The above-mentioned 209 g of the cyclized product crude product was dissolved in 400 mL of methanol,A one-time addition of the aqueous sodium hydroxide solution (34 g of sodium hydroxide dissolved in 140 mL of water)The reaction mixture was stirred at room temperature for 30 min (TLC monitoring).After completion of the reaction, the methanol was concentrated under reduced pressure. To the concentrated residue was added 100 mL of water, the aqueous phase was washed twice with 80 mL of ethyl acetate and the aqueous phase was cooled to T≤ 10 , slowly dropping concentrated hydrochloric acid to pH = 3-4. The extract was extracted with 150 mL of ethyl acetate three times to synthesize the organic phase with 150 mLSaturated with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give crude cyproterone. The ciprofloxacin crude product with 6g liveThe charcoal was decolorized and recrystallized from a mixed solvent of toluene 100 mL and n-hexane 300 mL to obtain 180 g of a pale yellow ciprofibrate product(V), the yield of 90percent, the total yield of 71percent.
With titanium tetrachloride; magnesium In tetrahydrofuran; dichloromethane at 0 - 120℃; for 2 h; Green chemistry
At 0 °C to 5g 2- methyl-2- (4-vinyl-phenoxy) propionic acid (III) was dissolved 40mL DCM + 4mLTHF, addthe magnesium 0.57g, 3.67g CCl4, 0.45g TiCl4, 0 The reaction was stirred at a constant temperature of 120 °C/min for 2 hours. The reaction solution was poured into a 100 mL saturated Na2SO4 solution and extracted with ethyl acetate. The organic phase was washed with a saturated NaCl solution, and the activated carbon was decolorized anddried over anhydrous Na2SO4 .The solvent was evaporated under reduced pressure and recrystallization from n-hexane gave 6.65 g of a white solid of ciprofibrate (IV) in a yield of 94.8percent.The total yield of the three-step reaction is 82.1percent. The crude product can be purified by decoloring with active carbon and recrystallization from n-hexane. The HPLC purity of the resulting cyproterol white crystals is 98.6percent.
Reference：
[1] Patent: CN106928047, 2017, A, . Location in patent: Paragraph 0022; 0054; 0055; 0056; 0063; 0071; 0079
4
[ 84443-44-7 ]
[ 52214-84-3 ]
Yield
Reaction Conditions
Operation in experiment
240 g
Stage #1: With potassium carbonate In methanol at 20℃; for 10 h; Stage #2: for 24 h; Reflux Stage #3: Alkaline conditions
The alcoholysis reaction: 1 mol of 4-(2,2-dichlorocyclopropyl)phenyl acetate, 300 g of methanol, was added to a 1L reaction flask.0.3 mol of potassium carbonate was reacted at 20° C. for 10 hours, and there was no raw material in the HPLC control, and was concentrated under reduced pressure to obtain about 250 g of an oil.Alkylation: Into a 2L clean reaction flask, 1.8 mol of ethyl bromoisobutyrate was added, 2 mol of potassium carbonate, 600 g of alcohol solution.The product was warmed at reflux for 24 hours. The raw material in HPLC was controlled to be 99percent.
3.5 Preparation of 2[-4-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid (ciprofibrate)
(5) 5 g of the ester obtained above, 20 ml of methanol and 0.84 g of sodium hydroxide are introduced into a 100 ml round-bottomed flask. The mixture is heated at 50°-60° C. for 2 h, with stirring and then concentrated under reduced pressure. The solid obtained is taken up with water and the aqueous solution is washed with ether and then acidified to pH 1 with hydrochloric acid. Extraction is carried out with ethyl acetate. The organic phase is washed with water and then dried and concentrated. The oil obtained crystallizes on the addition of cyclohexane. The solid obtained is recrystallized from toluene to give 3.6 g (yield=82%) of ciprofibrate melting at 115° C. Preparations I-VIII given above to illustrate the invention and the comparative examples show that the method according to the invention affords the following advantages:
...;C10) fatty acids, long-chain monounsaturated fatty acids, and dicarboxylic acids, particularly dodecanedioic acid. Also included are lower alkyl, preferably methyl, esters of the fibrates and lower alkyl, preferably methyl, esters of the fatty acids. Fibrates include: clofibrate: 2-(4-chlorophenoxy)-2-methylpropanoic acid ethyl ester fenofibrate: 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid isopropyl ester ciprofibrate: 2-(4-(2,2-dichlorocyclopropyl)phenoxy)isobutyric acid gemfibrozil: 2-(2,4-dimethylphenoxypropyl)-2-methylpropanoic acid bezafibrate: 2-(4-(4-chlorobenzoylaminoethyl)phenoxy)-2-methylpropanoic acid
A list including these and other examples of PPARα activators is as follows: ... 2-(3-chlorophenoxy)-2-methylpropanoic acid ethyl ester 2-(4-chlorophenoxy)-2-methylpropanoic acid ethyl ester 2-(4-(4-chlorophenyl)phenoxy)-2-methylpropanoic acid ethyl ester 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid isopropyl ester 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoic acid 2-(4-(4-chlorobenzoylaminoethyl)phenoxy)-2-methylpropanoic acid 2-(2,3-dimethyl-4-(1,2,3,4-tetrahydronaphth-1-yl)phenoxy)acetic acid 2-(2-methyl-3-ethyl-4-(4-chlorobenzyl)phenoxy)acetic acid ...
1 (1)-(-)-2-(4-(2,2-Dichlorocyclopropyl)phenoxy)-2-methylpropionic acid methyl ester
(1)-(-)-2-(4-(2,2-Dichlorocyclopropyl)phenoxy)-2-methylpropionic acid methyl ester (1)-(-)-2-(4-(2,2-Dichlorocyclopropyl)phenoxy)-2-methylpropionic acid (30 mg) in methanol (4.5 ml) and concentrated sulphuric acid (2 drops) were heated under reflux for 1.5 hours. The solution was concentrated by evaporation under reduced pressure and the residue dissolved in diethyl ether (10 ml), washed twice with saturated aqueous sodium hydrogen carbonate, water and brine, before being dried over anhydrous magnesium sulphate. The organic phase was removed by evaporation under reduced pressure to afford the desired (1)-(-)-2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropionic acid methyl ester as a white solid (22 mg). Under the hplc conditions described above, the (1)-(-)-2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropionic acid methyl ester was analyzed as having an excess of the desired enantiomer over the racemate of 95.5%.
2 (-)-2-[4-(2,2-Dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid
(-)-2-[4-(2,2-Dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid The crude (-)-4-(2,2-dichlorocyclopropyl)phenol (4.6 g) from the previous reaction was dissolved in acetone (63.2 ml) and added slowly to a solution of sodium hydroxide (6.7 g, 0.17 mol) in acetone (42 ml) under reflux. After 15 minutes, chloroform (1.5 g, 0.013 mol) in acetone (25 ml) was added at a rate which maintained a gentle reflux. After one hour, the solvent was removed by evaporation under reduced pressure and the resulting solid partitioned between distilled water (350 ml) and diethyl ether (100 ml). The organic phase was removed and the aqueous phase acidified with dilute hydrochloric acid and extracted with diethyl ether (2*100 ml). The combined ethereal extracts were washed with water, dried with anhydrous magnesium sulphate and the solvent removed by evaporation under reduced pressure to afford the crude product (3.5 g). This material was chromatographed on silica gel eluding with diethyl ether/hexane/glacial acetic acid (4:15:1) to afford (-)-2-[4-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid (0.5 g) with properties identical with that obtained by the described resolution of racemic material with (-)-α-methylbenzylamine. A sample of this material was methylated and analyzed by chiral HPLC, as described for the resolved material, and found to have an enantiomeric ratio of greater than 95:5 in favour of the (-)-enantiomer.
With sodium hydroxide
24 [I; A and A' are CH3, R, R1, R3, R3' and Q are H, R2 and R2' are Cl, and n is 0; para orientation].
[I; A and A' are CH3, R, R1, R3, R3' and Q are H, R2 and R2' are Cl, and n is 0; para orientation]. A mixture of 8 g. (0.0356 mole) of p-(2,2-dichlorocyclopropyl)phenol, 11.2 g. (0.28 mole) of sodium hydroxide pellets, 11 g. of chloroform and 350 ml. of acetone was prepared at 0°C. The cooling bath was removed, the mixture stirred for a minute and then heated on a steam bath to reflux temperature. The reaction mixture was stirred at reflux for three hours and then concentrated in vacuo. The residual gum was partitioned between dilute hydrochloric acid and ether, and the ether layer was separated, dried and concentrated in vacuo. The residual oil (14 g.) was partitioned between dilute aqueous sodium bicarbonate and ether. The sodium bicarbonate solution was acidified with concentrated hydrochloric acid and extracted with ether. The ether solution was dried over anhydrous sodium sulfate and concentrated. The residue (9.5 g. of yellow oil) was crystallized twice from hexane to give 6.0 g. of 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionic acid in the form of a pale cream-colored solid, m.p. 114°-116°C.
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4h;
7 Preparation of Compound 07
1 g of 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoic acid, 0.57 g of dicyclohexylcarbodiimide, 0.5 g of 2-amino-1-(4-hydroxyphenyl)ethyl ketone and 60 ml of dichloromethane were placed into the 100 ml single-neck flask, reacted for 4 hours at room temperature, evaporated to dryness, then purified through chromatography on silica gel column, to give the target compound (760 mg). MS (ESI): 422 (M+H+). 1H-NMR: 7.899-7.877 (1H, d), 7.720 (1H, s), 7.167-7.147 (4H, m), 6.992-6.892 (4H, m), 4.732-4.711 (2H, d), 1.953 (1H, m), 1.554 (6H, s), 1.225 (2H, m).
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4h;
8 Preparation of Compound 08
2 g of 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoic acid, 1.2 g of dicyclohexylcarbodiimide, 0.6 g of 2-amino-1-(4-hydroxyphenyl)ethyl ketone and 60 ml of dichloromethane were placed into the 100 ml single-neck flask, reacted for 4 hours at room temperature, evaporated to dryness, then purified through chromatography on silica gel column, to give the target compound (1.15 g). MS (ESI): 694 (M+H+). 1H-NMR: 8.085-8.064 (1H, d), 7.987-7.967 (2H, d), 7.169-7.026 (6H, m), 6.982-6.916 (4H, m), 4.764-4.753 (2H, d), 2.866-2.820 (2H, m), 1.755 (12H, m), 1.599-1.437 (4H, m).
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4h;
7.07 Experiment 7 Preparation of Compound 07
Experiment 7 Preparation of Compound 07 [0084] 1 g of 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoic acid, 0.57 g of dicyclohexylcarbodiimide, 0.5 g of 2-amino-1-(4-hydroxyphenyl)ethyl ketone and 60 ml of dichloromethane were placed into the 100 ml single-neck flask, reacted for 4 hours at room temperature, evaporated to dryness, then purified through chromatography on silica gel column, to give the target compound (760 mg). MS (ESI): 422 (M+H+). 1H-NMR: 7.899-7.877 (1H, d), 7.720 (1H, s), 7.167-7.147 (4H, m), 6.992-6.892 (4H, m), 4.732-4.711 (2H, d), 1.953 (1H, m), 1.554 (6H, s), 1.225 (2H, m).
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4h;
8.08 Experiment 8 Preparation of Compound 08
Experiment 8 Preparation of Compound 08 [0085] 2 g of 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoic acid, 1.2 g of dicyclohexylcarbodiimide, 0.6 g of 2-amino-1-(4-hydroxyphenyl)ethyl ketone and 60 ml of dichloromethane were placed into the 100 ml single-neck flask, reacted for 4 hours at room temperature, evaporated to dryness, then purified through chromatography on silica gel column, to give the target compound (1.15 g). MS (ESI): 694 (M+H+). 1H-NMR: 8.085-8.064 (1H, d), 7.987-7.967 (2H, d), 7.169-7.026 (6H, m), 6.982-6.916 (4H, m), 4.764-4.753 (2H, d), 2.866-2.820 (2H, m), 1.755 (12H, m), 1.599-1.437 (4H, m).
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 12h;
General procedure: To a solution of 2-bromo-4-hydroxyacetophenone 11 (20.0 mmol) in tetrahydrofuran (THF) (50 mL), hexamethylenetetramine(20.0 mmol) was added and stirred for 3 h at room temperature, and then the precipitated hexamethylenetetramine adduct 12 was filtered out. The adduct 12 was then heated with ethanol (80 mL) and concentrated HCl (8 mL) for 1 h at 45 C. After cooling, the inorganics were filtered out, the mixture was washed with ethanol (20 mL), and the solvent was distilled out completely under reduced pressure to obtain the desired compound 13. Then 14a-d (2.0 mmol), triethylamine (4.0 mmol), and EDCI·HCl (4.0 mmol), followed by HOBT (4.0 mmol), were added to a stirred solution of 13 (2.0 mmol) in CH2Cl2 (10 mL) and the mixture was stirred for 12 h at room temperature. Saturated Na2CO3 was added, the mixture was extracted with ethyl acetate, and the extracts were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by chromatography to give target compounds 15a-d.
With sodium hydroxide In ethanol at 20℃; for 0.5h;
3.4 Preparation of ciprofibrate (V)
The above crude 265K cyclization product (IV) and 400Kg of ethanol were withdrawn in a 1000 L reaction ax,Open mechanical agitation,One-time pumping has been equipped with a good solution of sodium hydroxide (40Kg sodium hydroxide dissolved in 195Kg water),Room temperature reaction 30 min (HPLC monitoring).After completion of the reaction, the ethanol was concentrated under reduced pressure.100Kg of water was poured into the concentrated ax, the aqueous phase was washed twice with 90Kg ethyl acetate, the aqueous phase was cooled to T? 10C, and concentrated hydrochloric acid was slowly added dropwise to pH = 3-4.The aqueous phase was extracted three times with 200 Kg of ethyl acetate. The organic phase was synthesized, washed with 200 Kg of saturated brine, dried over 30 Kg of anhydrous sodium sulfate, filtered and concentrated to give crude cyproterone.The crude ciprofibrate was decolored with 10 Kg of activated carbon,87 Kg of toluene and 275 Kg of n-hexane mixed solvent232Kg light yellow ciprofibric products (), the yield of 92%, the total yield of 88%.
91%
With sodium hydroxide In ethanol; water at 20℃; for 0.5h; Large scale;
3 Preparation of Ciprofibrate (V)
The above 274Kg of the cyclized product crude and 500Kg of ethanol were pumped into a 1000L reaction ax and mechanical stirring was started. A good aqueous sodium hydroxide solution (41Kg sodium hydroxide dissolved in 200Kg water) was drawn in one time and reacted at room temperature for 30min monitor). After the reaction was completed, the ethanol was concentrated under reduced pressure. The concentrated ax was cooled to 10 ° C, concentrated hydrochloric acid was slowly dropped acidified to pH = 3-4. The aqueous phase was extracted three times with 200Kg of ethyl acetate, and the organic phase was synthesized, washed with 200Kg of saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated to obtain crude ciprofibrate. The crude ciprofibrate was decolorized with lOKg of activated carbon, and recrystallized from a mixed solvent of 200Kg of toluene and 200Kg of n-hexane to obtain 260Kg of light yellow ciprofibrate (V) in a yield of 91%. The total yield86%
Multi-step reaction with 3 steps
1: potassium carbonate / acetonitrile / 48 h / 20 °C
2: trimethyldodecylammonium chloride; sodium hydroxide / 24 h / 20 °C
3: sodium hydroxide / methanol; water / 0.5 h / 20 °C
Multi-step reaction with 3 steps
1: caesium carbonate / acetonitrile / 24 h / 20 °C
2: sodium hydroxide; tetrabutylammomium bromide / 12 h / 0 - 20 °C
3: sodium hydroxide / ethanol / 0.5 h / 20 °C
Multi-step reaction with 3 steps
1: caesium carbonate / acetonitrile / 12 h / 20 °C
2: sodium hydroxide; tetrabutylammomium bromide / chloroform / 12 h / 0 - 20 °C / Autoclave; Large scale
3: sodium hydroxide / ethanol; water / 0.5 h / 20 °C / pH 3 - 4 / Large scale
With sodium hydroxide In methanol; water at 20℃; for 0.5h;
2.4 Preparation of ciprofibrate (V)
The above-mentioned 209 g of the cyclized product crude product was dissolved in 400 mL of methanol,A one-time addition of the aqueous sodium hydroxide solution (34 g of sodium hydroxide dissolved in 140 mL of water)The reaction mixture was stirred at room temperature for 30 min (TLC monitoring).After completion of the reaction, the methanol was concentrated under reduced pressure. To the concentrated residue was added 100 mL of water, the aqueous phase was washed twice with 80 mL of ethyl acetate and the aqueous phase was cooled to T≤ 10 , slowly dropping concentrated hydrochloric acid to pH = 3-4. The extract was extracted with 150 mL of ethyl acetate three times to synthesize the organic phase with 150 mLSaturated with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give crude cyproterone. The ciprofloxacin crude product with 6g liveThe charcoal was decolorized and recrystallized from a mixed solvent of toluene 100 mL and n-hexane 300 mL to obtain 180 g of a pale yellow ciprofibrate product(V), the yield of 90%, the total yield of 71%.
2-methyl-2-(4-vinylphenoxy)propionic acid[ No CAS ]
[ 52214-84-3 ]
Yield
Reaction Conditions
Operation in experiment
98.6 %Chromat.
With titanium tetrachloride; magnesium In tetrahydrofuran; dichloromethane at 0 - 120℃; for 2h; Green chemistry;
1.3 (3) Synthesis of ciprofibrate (IV)
At 0 °C to 5g 2- methyl-2- (4-vinyl-phenoxy) propionic acid (III) was dissolved 40mL DCM + 4mLTHF, addthe magnesium 0.57g, 3.67g CCl4, 0.45g TiCl4, 0 The reaction was stirred at a constant temperature of 120 °C/min for 2 hours. The reaction solution was poured into a 100 mL saturated Na2SO4 solution and extracted with ethyl acetate. The organic phase was washed with a saturated NaCl solution, and the activated carbon was decolorized anddried over anhydrous Na2SO4 .The solvent was evaporated under reduced pressure and recrystallization from n-hexane gave 6.65 g of a white solid of ciprofibrate (IV) in a yield of 94.8%.The total yield of the three-step reaction is 82.1%. The crude product can be purified by decoloring with active carbon and recrystallization from n-hexane. The HPLC purity of the resulting cyproterol white crystals is 98.6%.
4-(2,2-dichlorocyclopropyl)phenyl acetate[ No CAS ]
[ 52214-84-3 ]
Yield
Reaction Conditions
Operation in experiment
240 g
Stage #1: 4-(2,2-dichlorocyclopropyl)phenyl acetate With potassium carbonate In methanol at 20℃; for 10h;
Stage #2: bromoethyl isobutyrate In methanol for 24h; Reflux;
Stage #3: With water Alkaline conditions;
1 Example 1
The alcoholysis reaction: 1 mol of 4-(2,2-dichlorocyclopropyl)phenyl acetate, 300 g of methanol, was added to a 1L reaction flask.0.3 mol of potassium carbonate was reacted at 20° C. for 10 hours, and there was no raw material in the HPLC control, and was concentrated under reduced pressure to obtain about 250 g of an oil.Alkylation: Into a 2L clean reaction flask, 1.8 mol of ethyl bromoisobutyrate was added, 2 mol of potassium carbonate, 600 g of alcohol solution.The product was warmed at reflux for 24 hours. The raw material in HPLC was controlled to be 99%.
8
Add 1g of drug molecules (Ciprofibrate) (0.5 mmol, 144.6mg) and methanol containing 40mol% tert-butyl nitrite to the reaction test tube; then react for 48 hours at 40°C in the air; after the reaction, add sulfur Stir and quench with sodium sulfite, remove the solvent with a rotary evaporator, adsorb on silica gel, and finally perform column chromatography with a mixed solvent of ethyl acetate and petroleum ether to obtain 3g of the product, with a yield of 79%
79%
With tert.-butylnitrite at 40℃; for 48h; Green chemistry;
With Ir(dFFppy)<SUB>2</SUB>(dtbbpy)PF<SUB>6</SUB>; lithium carbonate In dimethyl sulfoxide at 35℃; for 48h; Inert atmosphere; Irradiation; Sealed tube;
With 1,1,1,3',3',3'-hexafluoro-propanol; water-d2; palladium diacetate; N-(2-(dimethylamino)ethyl)-2,4,6-triisopropylbenzamide; silver carbonate at 90℃; for 24h; Schlenk technique;
cyclobutanone O-(tert-butoxycarbonyl)oxime[ No CAS ]
(E)-7-cyano-1-phenylhept-1-en-3-yl 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H24N2O2 In dichloromethane at 20℃; for 4h; Inert atmosphere; Schlenk technique; Irradiation;
cyclobutanone O-(tert-butoxycarbonyl)oxime[ No CAS ]
(R,E)-7-cyano-1-phenylhept-1-en-3-yl 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With tetrakis(actonitrile)copper(I) hexafluorophosphate; (4R,4'R)-2,2'-(cyclopentane-1,1-diyl)-bis(4-phenyl-4,5-dihydrooxazole) In dichloromethane at 20℃; for 4h; Inert atmosphere; Schlenk technique; Irradiation; enantioselective reaction;
With dmap; diisopropyl-carbodiimide In dichloromethane at 25 - 30℃; Inert atmosphere;
88 %
With trifluoromethanesulfonylpyridinium salt; triethylamine In dichloromethane at 20℃;
43 Example 43
In a 25mL reaction tube were added ciprofibrate (1.0mmol, 288.1mg), base Et3N (1.8mmol, 182.1mg) and 5mL of dichloromethane, followed by the addition of trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.7mmol , 755.0mg) and N-hydroxyphthalimide (1.2mmol, 195.7mg), stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product ester was separated by column chromatography with a yield of 88%.
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃;
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt; pinacolborane In dichloromethane at 25℃; Schlenk technique; Inert atmosphere;
62 %
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt; pinacolborane In dichloromethane at 20℃; Inert atmosphere; Schlenk technique;
45 Example 45
Under a nitrogen atmosphere, ciprofibrate (1.0 mmol, 288.0 mg), 1-pyridine-4-piperidine (1.6 mmol, 259.2 mg) and 5 mL of dichloromethane were added to a 25 mL Schlenk tube, followed by Trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.7mmol, 755mg) and HBpin (1.1mmol, 140.8mg) were added sequentially at intervals, and stirred for 10min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product aldehyde compound was obtained by column chromatography separation with a yield of 62%.
With 4-piperidinylpyridine; DBpin; trifluoromethanesulfonylpyridinium salt In dichloromethane at 25℃; Schlenk technique; Inert atmosphere;
66 %
With 4-piperidinylpyridine; DBpin; trifluoromethanesulfonylpyridinium salt In dichloromethane at 20℃; Inert atmosphere; Schlenk technique;
64 Example 64
Under nitrogen, in a 25 mL Schlenk tube were added naproxen (0.3 mmol, 69.1 mg), 1-pyridine-4-piperidine (0.48 mmol, 77.8 mg) and 2 mL of dichloromethane, followed by Add trifluoromethanesulfonylpyridinium salt PPDP-Tf (0.51mmol, 226.5mg) and DBpin (0.33mmol, 42.5mg) successively, and stir for 10min. After the reaction was completed, aqueous solution and dichloromethane (3×3 mL) were added to the system for extraction, and the product aldehyde compound was obtained by column chromatography separation with a yield of 69%.
With trifluoromethanesulfonylpyridinium salt; triethylamine In dichloromethane at 20℃;
57 Example 57
In a 25mL reaction tube was added ciprofibrate (1.0mmol, 288.1mg), base Et3N (1.8mmol, 182.1mg) and 5mL of dichloromethane, followed by the addition of trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.7mmol , 755.0mg) and dehydroepiandrosterone (1.2mmol, 346.1mg), stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product ester was obtained by column chromatography separation with a yield of 98%.
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt In dichloromethane at 20℃;
16 Example 16
In a 25mL reaction tube, add ciprofibrate (1.0mmol, 288.0mg), tert-butylamine (1.2mmol, 87.7mg),1-Pyridine-4-piperidine (1.5mmol, 243.1mg) and 5mL of dichloromethane were added, followed by trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.2mmol, 532.8mg), and stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product amide was separated by column chromatography with a yield of 86%.
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt In dichloromethane at 20℃;
17 Example 17
Add ciprofibrate (1.0mmol, 288.0mg) in a 25mL reaction tube, 1-adamantanamine(1.2mmol, 181.4mg),1-Pyridine-4-piperidine (1.5mmol, 243.1mg) and 5mL of dichloromethane were added, followed by trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.2mmol, 532.8mg), and stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product amide was separated by column chromatography with a yield of 86%.
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt In dichloromethane at 20℃;
18 Example 18
In a 25mL reaction tube, add ciprofibrate (1.0mmol, 288.0mg), 4-ethynylaniline (1.2mmol, 140.5mg),1-Pyridine-4-piperidine (1.5mmol, 243.1mg) and 5mL of dichloromethane were added, followed by trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.2mmol, 532.8mg), and stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product amide was separated by column chromatography with a yield of 88%.
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt In dichloromethane at 20℃;
19 Example 19
In a 25mL reaction tube, add ciprofibrate (1.0mmol, 288.0mg), 9-aminoacridine (1.2mmol, 232.9mg),1-Pyridine-4-piperidine (1.5mmol, 243.1mg) and 5mL of dichloromethane were added, followed by trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.2mmol, 532.8mg), and stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product amide was separated by column chromatography with a yield of 53%.
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt In dichloromethane at 20℃;
20 Example 20
In a 25mL reaction tube, add ciprofibrate (1.0mmol, 288.0mg), 9,9-diphenyl-2-aminofluorene (1.2mmol, 399.8mg),1-Pyridine-4-piperidine (1.5mmol, 243.1mg) and 5mL of dichloromethane were added, followed by trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.2mmol, 532.8mg), and stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product amide was separated by column chromatography with a yield of 97%.
With 4-piperidinylpyridine; trifluoromethanesulfonylpyridinium salt In dichloromethane at 20℃;
23 Example 23
Add ciprofibrate (1.0mmol, 249.1mg) in a 25mL reaction tube,Dimethylhydroxylamine hydrochloride (1.2mmol, 116.4mg), 1-pyridine-4-piperidine (2.7mmol, 437.6mg) and 5mL of dichloromethane, then added trifluoromethanesulfonylpyridinium salt PPDP-Tf (1.2mmol , 532.8mg), stirred for 5min. After the reaction was completed, aqueous solution and dichloromethane (3×5 mL) were added to the system for extraction, and the product amide was separated by column chromatography with a yield of 94%.
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