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CAS No. : | 98-11-3 |
Formula : | C6H6O3S |
M.W : | 158.18 |
SMILES Code : | O=S(C1=CC=CC=C1)(O)=O |
MDL No. : | MFCD00011689 |
InChI Key : | SRSXLGNVWSONIS-UHFFFAOYSA-N |
Pubchem ID : | 7371 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H290-H314 |
Precautionary Statements: | P260-P280-P303+P361+P353-P304+P340+P310-P305+P351+P338 |
Class: | 8 |
UN#: | 2583 |
Packing Group: | Ⅱ |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; diethyl ether; for 48h; | The E-2-METHOXY-N- (3- {4- [3-METHYL-4- (6-METHYL-PYRIDIN-3-YLOXY)-PHENYLAMINO]- QUINAZOLIN-6-YL}-ALLYL)-ACETAMIDE monobesylate was prepared as the following. The E-2- METHOXY-N- (3- {4- [3-METHYL-4- (6-METHYL-PYRIDIN-3-YLOXY)-PHENYLAMINO]-QUINAZOLIN-6-YL}-ALLYL)- acetamide free base, prepared according to the method of either Example 1, 2 or 3 was dissolved 500 mg in THF. BENZENESULFONIC acid (168mg, 1 molar equivalent) was added to the free base solution. Diethyl ether was then added dropwise to the solution until cloudiness was observed. After overnight stirring, the precipitate oiled out on the sides of the flask. The oily material was scraped free and allowed to stir for an additional day. Crystalline material was collected after two days. The monobesylate had a melting onset at 135C by DSC, and a peak m. p. of 137C. The material was evaluated for hygroscopicity in relative humidity chambers. After 16 hours in the 75% RH chamber there was no significant water sorption. The 94% RH chamber caused a 6.7% weight increase after the same time period, and deliquescence was observed after 16 hours in a 100% relative humidity chamber. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | In ethanol;Heating; | The compound of Example 1 as a free base (2.25 g) was suspended in ethanol (50 mL) and benzensulfonic acid (0.737 g) in ethanol (50 mL) was added. The mixture was heated with vigorous stirring. All solid material dissolved to give a reddish solution. The solution was allowed to cool to room temperature and the flask scratched. Crystal formation was slow, some seeds were found, added to solution and placed in freezer overnight. Grayish- tan solids had formed in the flask; the materia. was broken up & collected by suction filtration. The solids were washed with ethanol, then hexane and air- dried. Weighed product: 2.05 g, 69% yield. Melting point: 213 CElemental Analysis:Calcd. FoundC 50.59 50.24H 3.30 3.50N 8.74 8.54F 11.86 11.79Cl 5.53 5.63 S 5.00 5.16. |
69% | In ethanol;Heating; | The compound of Example 1 as a free base (2.25 g) was suspended in ethanol (50 ml_) and benzensulfonic acid (0.737 g) in ethanol (50 ml_) was added. The mixture was heated with vigorous stirring. All solid material dissolved to give a reddish solution. The solution was allowed to cool to room temperature and the flask scratched. Crystal formation was slow, some seeds were found, added to solution and placed in freezer overnight. Grayish-tan solids had formed in the flask; the material was broken up & collected by suction filtration. The solids were washed with ethanol, then hexane and air-dried. Weighed product: 2.05 g, 69% yield. <n="18"/>Melting point: 213 0CElemental Analysis:Calcd. FoundC 50.59 50.24H 3.30 3.50N 8.74 8.54F 11.86 11.79Cl 5.53 5.63S 5.00 5.16. |
69% | In ethanol;Heating / reflux; | Example 4 Preparation of 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide phenylsulfonate The compound of Example 1 as a free base (2.25 g) was suspended in ethanol (50 mL) and benzensulfonic acid (0.737 g) in ethanol (50 mL) was added. The mixture was heated with vigorous stirring. All solid material dissolved to give a reddish solution. The solution was allowed to cool to room temperature and the flask scratched. Crystal formation was slow, some seeds were found, added to solution and placed in freezer overnight. Grayish-tan solids had formed in the flask; the material was broken up & collected by suction filtration. The solids were washed with ethanol, then hexane and air-dried. Weighed product: 2.05 g, 69% yield. Melting point: 213 C. |
69% | In ethanol;Heating; | Example 4: Preparation of 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3- fluorophenoxy}-pyridine-2-carboxylic acid methylamide phenylsulfonate; The compound of example 1 as a free base (2.25 g) was suspended in ethanol (50 mL) and benzensulfonic acid (0.737 g) in ethanol (50 mL) was added. The mixture was heated with vigorous stirring. All solid material dissolved to give a reddish solution. The solution was allowed to cool to room temperature and the flask scratched. Crystal formation was difficult to achieve, some seeds were found, added to solution and placed in freezer overnight. Grayish-tan solids had formed in the flask; the material was broken up & collected by suction filtration. The solids were washed with ethanol, then hexane and air-dried. Weighed product: 2.05 g, 69% yield.Melting point: 213 CElemental Analysis: Calcd. Foundc 50.59 50.24H 3.30 3.50N 8.74 8.54F 11.86 11.79CI 5.53 5.63s 5.00 5.16 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In Isopropyl acetate; at 20 - 32.5℃; for 23 - 24h;Product distribution / selectivity; | 10.0 g of Compound 1 and 70 ml isopropyl acetate were charged into a reactor. 5.25 g anhydrous benzenesulfonic acid was dissolved into 30 ml of isopropyl acetate using a 2nd reactor. The solution of benzenesulfonic acid was charged into the slurry of Compound 1. The resulting slurry was stirred at room temperature for 23 hrs and isolated by filtration. The cake was washed with isopropyl acetate and dried in a vacuum oven at 45 C +/- 5 0C to provide Form X.A sample of Form X was analyzed using a plurality of analytical techniques. Figures 36 and 37 depict an experimental XRPD of Form X and a DSC of Form X. The XRPD was recorded on a Corundum calibrated Bruker D8 Advance diffractometer with a Vantac line detector. The 2 Theta range was approximately 2 degrees to 40 degrees, with a step size of 0.014 degrees. The time per step was approximately 105 milliseconds. Cu Ka seal tube radiation was used at 40 kV, 4OmA under ambient conditions.; Compound 1 was added to reactor A with 10 vol of isopropyl acetate. In a separate reactor, benzenesulfonic acid monohydrate (0.95 eq based on anhydrous Benzenesulfonic acid) was dissolved with 10 vol of isopropyl acetate. The benzenesulfonic acid solution was <n="52"/>then added to reactor A. The resulting slurry was heated to 30 0C +/- 2.5 0C and stirred for 24 h. The mixture was cooled to 20.0 0C +/- 50C, the solids filtered and washed with 5 vol isopropyl acetate. The washed solids were dried at 30 0C in a fluidized bed with N2 bleed to provide Form XIII.A sample of Form XIII was analyzed using a plurality of analytical techniques. Figures 43-45 depict an experimental XRPD of Form XIII, a DSC of Form XIII and a TGA of Form XIII, respectively. The XRPD was recorded on a Corundum calibrated Bruker D8 Advance diffractometer with Vantac line detector. The 2 Theta range was approximately 2 degrees to 40 degrees, with a step size of 0.014 degrees. The time per step was approximately 105 milliseconds. Cu Ka seal tube radiation was used at 40 kV, 4OmA under ambient conditions. The TGA was recorded as described above except that data was recorded out to 35O0C.; Form XV 4.94 g of Compound 1 and 24.7 ml isopropyl acetate were charged to reactor A. 1.195 g (0.6 eq) benzenesulfonic acid hydrate and 24.7 ml isopropyl acetate was charged to reactor B. Reactor B contents were charged to reactor A at ambient temperature. The resulting slurry was stirred at room temperature for 23 hrs followed by <n="53"/>filtration and a wash with isopropyl acetate. The cake was dried in a vacuum oven to provide Form XV.A sample of Form XV was analyzed using a plurality of analytical techniques. Figure 49 depicts an experimental XRPD of Form XV. The XRPD was recorded on a Corundum calibrated Bruker D8 Advance diffractometer with Vantac line detector. The 2 Theta range was approximately 2 degrees to 40 degrees, with a step size of 0.014 degrees. The time per step was approximately 105 milliseconds. Cu Ka seal tube radiation was used at 40 kV, 4OmA under ambient conditions. | |
In toluene; at 82.5 - 87.5℃; for 18h;Product distribution / selectivity; | 43.6 g of Benzenesulfonic acid monohydrate was charged into reactor A. 2.00 L of Toluene (20.0 vol) was added to reactor A. The resulting mixture was heated to reflux, and concentrated to '/z volume (1.00 L). The concentrated mixture was cooled to 75C +/- 2.5 0C, followed by the addition of 1.00 L Toluene (10.0 vol). This mixture was cooled to 40C +/- 2.5 C. 100 g of Compound 1 (1.0 eq) was added to reactor B followed by the addition of the Benzenesulfonic acid / Toluene solution from reactor A. The resulting slurry was heated to 85C +/- 2.5C and stirred for a total of 18 hours at 85C +/- 2.5C. The slurry was cooled to 20.0 0C +/- 5 0C, solids were filtered, and washed with Toluene (1.00 L, 10 vol). The material was dried in a vacuum oven at 45 C +/- 5 0C to provide Form XII.A sample of Form XII was analyzed using a plurality of analytical techniques. Figures 40-42 depict an experimental XRPD of Form XII, a DSC of Form XII and a TGA of Form XII, respectively. The XRPD was recorded on a Corundum calibrated Bruker D8 Advance diffractometer with Vantac line detector. The 2 Theta range was approximately 2 degrees to 40 degrees, with a step size of 0.014 degrees. The time per step was approximately 105 milliseconds. Cu Ka seal tube radiation was used at 40 kV, 4OmA under ambient conditions. The TGA was recorded as described above except that data was recorded out to 35O0C. | |
In acetonitrile; at 60℃; for 3h;Product distribution / selectivity; | 12.1 g of anhydrous Benzenesulfonic acid and 24.92 g Compound 1 was charged into reactor. 250 ml Acetonitrile was added. The resulting slurry was heated to 60C for 3 hrs. This mixture was cooled to room temperature. The slurry was filtered, and washed with <n="51"/>acetonitrile. The material was re-suspended in the filtrate, and heated to 85C for 2 hrs, then cooled to room temperature and isolated by filtration. The wet cake was again re-suspended in 250 ml acetonitrile this time, and 12.0 g anhydrous benzenesulfonic acid was charged into the reactor. The resulting slurry was heated to 60C for 4 hrs followed by cooling to 40C for 2 hrs and then cooling to room temperature, and isolated by filtration. The cake was washed with acetonitrile and dried in a vacuum oven at 45 0C +/- 5 0C to provide Form XI.A sample of Form XI was analyzed using a plurality of analytical techniques. Figures 38 and 39 depict an experimental XRPD of Form XI and a DSC of Form XI, respectively. The XRPD was recorded on a Corundum calibrated Bruker D8 Advance diffractometer with Vantac line detector. The 2 Theta range was approximately 2 degrees to 40 degrees, with a step size of 0.014 degrees. The time per step was approximately 105 milliseconds. Cu Ka seal tube radiation was used at 40 kV, 4OmA under ambient conditions. |
In 2-methyltetrahydrofuran; Isopropyl acetate;Heating / reflux;Product distribution / selectivity; | 15.0 g of Compound 1 and 120 ml 2-methyltetrahydrofuran were charged to reactorA. 7.25 g benzenesulfonic acid hydrate and 180 ml isopropyl acetate was charged to reactorB. Reactor B contents were dried via azeotrope (solvent swap with fresh isopropyl acetate) twice to provide a dry solution of benzenesulfonic acid in isopropyl actete. Reactor B contents were charged into reactor A at ambient temperature. The resulting slurry was heated to reflux (homogeneous solution attained), and then cooled immediately to ambient temperature to afford a slurry. The slurry was concentrated under reduced pressure to Vi volume, followed by addition of isopropyl acetate to achieve the original volume. The concentration and suspension in isopropyl acetate was repeated followed by concentration to Vi volume, filtration, and a washed with isopropyl acetate. The cake was dried in a vacuum oven at 50 C to provide Form XIV.A sample of Form XIV was analyzed using a plurality of analytical techniques. Figures 47 and 48 depict an experimental XRPD of Form XIV and a DSC of Form XIV, respectively. The XRPD was recorded on a Corundum calibrated Bruker D8 Advance diffractometer with Vantac line detector. The 2 Theta range was approximately 2 degrees to 40 degrees, with a step size of 0.014 degrees. The time per step was approximately 105 milliseconds. Cu Ka seal tube radiation was used at 40 kV, 4OmA under ambient conditions. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; In Isopropyl acetate; at 20℃; for 18h;Product distribution / selectivity; | Form XVI 13.15 g of Compound l«besylate and 98.6 ml ethyl acetate were charged to reactor A. 21.04 g benzenesulfonic acid hydrate and 98.6 ml isopropyl acetate was charged to reactor B. Reactor B contents were charged to reactor A at ambient temperature. The resulting slurry was stirred at room temperature for 18 hrs followed by filtration and a wash with isopropyl acetate. The cake was dried in a vacuum oven at 35 0C to provide Form XVI.A sample of Form XVI was analyzed using a plurality of analytical techniques. Figures 50-52 respectively depict an experimental XRPD of Form XVI, a TGA trace of Form XVI, a DSC of Form XVI, and a DVS of Form XVI, each of which were obtained using the methods described above. The XRPD was recorded on a Corundum calibrated Bruker D8 Advance diffractometer with Vantac line detector. The 2 Theta range was approximately 3 degrees to 41 degrees, with a step size of 0.014 degrees. The time per step was approximately 105 milliseconds. Cu Ka seal tube radiation was used at 40 kV, 35mA under ambient conditions. The TGA was recorded as described above except that data was recorded out to 35O0C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In methanol; isopropyl alcohol; at 55℃; | Example 5 Preparation of 2-Fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazolo[1,2-b][1,2,4]triazin-2-yl]benzamide dibenzenesulfonic acid salt A suspension of 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazolo[1,2-b][1,2,4]triazin-2-yl]benzamide (500 mg, 1.212 mmol) in methanol (MeOH, 12 mL) was heated to 55 C. before a premixed solution of benzenesulfonic acid (578 mg, 3.65 mmol, 3.01 equiv) in isopropyl alcohol (IPA, 3.66 mL) was added dropwise at 55 C. The resulting clear solution was stirred at 55 C. for 30 min before methyl tert-butyl ether (MTBE, 12 mL) was added dropwise via an additional funnel. The solids were slowly precipitated out after addition of methyl tert-butyl ether. The resulting mixture was stirred at 55 C. for one an additional hour before being gradually cooled down to room temperature. The mixture was stirred at room temperature overnight. The solids were collected by filtration, washed with methyl tert-butyl ether (MTBE, 2*10 mL), and dried in vacuum oven at 45-55 C. to constant weight. The desired dibenzenesulfonic acid product (848 mg, 883.3 mg theoretical, 96% yield) was obtained as off-white crystalline solids. M.p. (decom.) 270.5 C.; 1H NMR (400 MHz, DMSO-d6) delta ppm 9.51 (s, 1H), 9.30 (dd, 1H, J=5.4 Hz, 1.4 Hz), 9.13 (d, 1H, J=8.3 Hz), 8.45 (m, 1H), 8.36 (d, 1H, J=0.9 Hz), 8.30 (s, 1H), 8.21 (dd, 2H, J=9.0 Hz, 1.8 Hz), 8.10-8.04 (m, 3H), 7.80 (dd, 1H, J=7.5 Hz, 8.3 Hz), 7.62-7.56 (m, 4H), 7.33-7.27 (m, 6H), 4.79 (s, 2H), 2.78 (d, 3H, J=4.5 Hz); 19F NMR (376.3 MHz, DMSO-d6) delta ppm -113.2; C23H17FN6O (free base, MW 412.42), LCMS (EI) m/e 413.0 (M++H) and 435.0 (M-+Na). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Compound of Formula (1) (0.50 g, 0. 8 mmol, 1.0 equiv) is dissolved in DCM (8 mL) and stirred with a 15% aqueous solution of sodium hydrosulfite (4 mL). The solution is stirred for 60 minutes. The organic layer was collected, washed with brine, and 2 mL (calc 0.2 mmol of hydroquinone) transferred to a round bottom flask. This solution was put under nitrogen. To this solution was added a solution of PhS03H in denatured IPA (0.200 mmol of PhS03H in 0.4 mL of IPA) dropwise. The resulting mixture was allowed to stir under nitrogen for 1 hour, at which point the mixture was concentrated and the crude mass was reslurried from EtOAc. The solid was collected by filtration and dried under reduced pressure to yield 0. 118 g of the desired product. | ||
Example 8: Preparation of the benzenesulfonate salt of the hydroquinone of <strong>[75747-14-7]17-AAG</strong>[0080] <strong>[75747-14-7]17-AAG</strong> (0.50 g, 0.8 mmol, 1.0 equiv) is dissolved in DCM (8 mL) and stirred with a 15% aqueous solution of sodium hydrosulfite (4 mL). The solution is stirred for 60 minutes. The organic layer was collected, washed with brine, and 2 rnL (calc 0.2 mmol of hydroquinone) transferred to a round bottom flask. This solution was put under nitrogen. To this solution was added a solution of PhSO3H in denatured IPA (0.200 mmol Of PhSO3H in 0.4 mL of IPA) dropwise. The resulting mixture was allowed to stir under nitrogen for 1 hour, at which point the mixture was concentrated and the crude mass was reslurried from EtOAc. The solid was collected by filtration and dried under reduced pressure to yield 0.118 g of the desired product 9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tert-butyl methyl ether; at 50 - 55℃;Inert atmosphere; | Example 1Compound 1 Compound 2; [0051] Compound 1 is prepared according to the method described in detail in at Example 20 of the '610 publication., the entirety of which is hereby incorporated herein by reference.[0052] The besylate salt of Compound 1, i.e., Compound 2, was prepared as follows.Compound 1 was added to MTBE under nitrogen to form a slurry and the mixture heated to50-55 C. Benzenesulfonic acid, in MTBE, was added and the resulting mixture stirred for one hour. The mixture was cooled to 0-5 C and allowed to stir for an hour. The resulting solids were collected by filtration and then dried at 65-70 C under vacuum to affordCompound 2. Characterization of the resulting material demonstrated that the Compound 2 was crystalline and this crystalline form referred to as Form P 1.[0053] FT-Raman spectrum for Compound 2, Form PI is depicted in Figure 1.[0054] PXRD for Compound 2, Form PI is depicted in Figure 2. Table 1 below sets out the X-ray diffraction peaks observed for Form P22 of compound 2 wherein each value is in degrees 2-theta.Table 1. Observed X-ray diffraction peaks for Compound 2 (Form PI)[0055] TG-FTIR for Compound 2, Form PI is depicted in Figure 3. The resulting thermogram shows the loss of about 0.9 weight % dichloromethane (residual solvent) in a step from 130-160 C.[0056] DSC for for Compound 2, Form P I is depicted in Figure 4 and Figure 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 45℃; | Benzenesulfonic acid 90% (160 mg, 0.90 mmol, 1.1 eq) was dissolved in THF (3 mL) at room temperature and was then added dropwise to a stirred solution of <strong>[500287-72-9]Rilpivirine</strong> base form II (300 mg, 0.82 mmol) in THF (6 mL, 20V) at 45C. Precipitation was observed. The reaction mixture was cooled to room temperature for 30 min and stirring was continued at the same temperature for 17 h. The reaction mixture was then filtered to give <strong>[500287-72-9]Rilpivirine</strong> benzenesulfonate Form 1. The filter cake was dried in a vacuum oven at 50C for 17 h. A white solid was obtained. XRD analysis of the solid indicated the same polymorphic form as was identified in the wet material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetone; at 20 - 50℃; for 18.5h; | The besylate salt of SRi can be prepared as follows: <strong>[1227633-49-9]4-(2-(2-(benzo[b]thiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)phenol</strong> free base (0.60 gram; 1.40 mmoles) aredissolved in 12 ml acetone at 50 C. A solution of benzenesulfonic acid (0.225 gram; 2.79 mmoles) in 1.2 ml acetone is added drop wise. Seed crystals are added at 48 C. and the crystallization takes place slowly. The suspension is allowed to cool over about 30 minutes to room temperature. The slurry is stirred for about 18 hours at room temperature and filtered. The salt is washed with 6 ml acetone in three portions and dried as described herein for other salts. The material has a melting point at about 219 C. with a melting enthalpy of 92 g/J.In another embodiment, the besylate salt of SRi comprises the following powder X-ray diffraction peaks (Angle 2-0.):6.2, 7.7, 17.7, 25.5; and which in an additional embodiment comprises the following powder X-ray diffraction peaks(Angle 2-0): 6.2,7.7, 15.2, 16.7, 17.1, 17.7, 19.8, 20.2,24.9, 25.2, 25.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2-methyltetrahydrofuran; acetonitrile; at 60℃; for 0.5h; | Preparation 1The aceton itrile solvate of 2-[(4S)-6-(4-chlorophenyl)- 1 -methyl-8-(methyloxy)-4H- [1 ,2,4]triazolo[4,3-a][1 ,4]benzodiazepin-4-yl]-N-ethylacetamide (for a preparation seeExample 1, 2.58 g)was slurried in acetonitrile (7 mL) and 2-methyltetrahydrofuran (7 mL). Benzenesulfonic acid (1.17 g) was dissolved in acetonitrile (7 mL). The resulting solution was charged to the slurry of 2-[(4S)-6-(4-ch lorophenyl)- 1 -methyl-8-(methyloxy)-4H- [1 ,2,4]triazolo[4 ,3-a][1 ,4]benzod iazepin-4-yl]-N-ethylacetamide acetonitrile solvate in acetonitrile and 2-methyltetrahydrofuran. An additional rinse of acetonitrile (1.4 mL) and 2-methyltetrahydruf ran (0.7 mL) was added to the slurry. The slurry was then warmed to 60 00 to dissolve. 2-methyltetrahydrofuran (50 mL) was then added over 30 minutes. Crystals formed during this addition. The resulting suspension was then cooled to 5 00 at a controlled, linear rate of 0.5 C/minute. The slurry was aged for 1 hour. The crystalline product was then isolated by filtration and rinsed with a 5 to 1 mixture of 2-methyltetrahydrofuran and acetonitrile (15 mL). The product was then dried in a vacuum oven at 55 00 overnight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.6% | A mixture of the compound of formula (4) (5.0 g, 10.4 mmol), benzenesulfonic acid (1.8 g, 11.4 mmol) and absolute ethanol (30 mL) Reaction kettle, cooling to -5 , through the hydrogen chloride to saturation, room temperature stirring 24h. Cooling to 0 , through the ammonia to saturation, white mixed Suspension, room temperature stirring 24h, Filtration, concentration of filtrate, water: dioxane = 1: 1 (20mL) room temperature beating 30min, filter, the filter cake, adding ethanol (45mL) to recrystallize, filter solid 6.3g, yield 92.6% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; | A solution of 4-chloromethyl-5-1,3-dioxolen-2-one(2.94 g, 20 mmol) was added to <strong>[42017-89-0]fenofibric acid</strong>(3.18 g, 10 mmol) and K2CO3 (2.76 g, 20 mmol) inN,N-dimethylacetamide (64 mL) at room temperatureat such a rate that the reaction maintained an internaltemperature of 60-65 C overnight. The reaction mixturewas cooled to 0 C and water (100 mL) was added slowly.The resulting mixture was stirred at room temperature for1.5 h, extracted with ethyl acetate (100 mL), and washedwith brine (150 mL × 3). The solvent was distilled offunder reduced pressure to obtain a residue. The residue waspurified further by column chromatography to give the titlecompounds. The following compounds were synthesizedaccording to this procedure. |
Tags: 98-11-3 synthesis path| 98-11-3 SDS| 98-11-3 COA| 98-11-3 purity| 98-11-3 application| 98-11-3 NMR| 98-11-3 COA| 98-11-3 structure
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P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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