Structure of 154477-54-0
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CAS No. : | 154477-54-0 |
Formula : | C15H19ClO3 |
M.W : | 282.76 |
SMILES Code : | CC(C)(C1=CC=C(C(CCCCl)=O)C=C1)C(OC)=O |
MDL No. : | MFCD09031254 |
InChI Key : | ULWORPZJUIFPIC-UHFFFAOYSA-N |
Pubchem ID : | 10062338 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
80% | With potassium hydrogencarbonate; potassium iodide In toluene at 80℃; for 30 h; Reflux | 1000 mL reaction flask, 55.4 g of diphenylpiperidine methanol was added successively, 42.1 g of potassium bicarbonate, 3.1g potassium iodide, 310 mL of toluene, Heated to 80 ° C, A solution of methyl 2- (4- (4-chlorobutyryl) phenyl) -2-methylpropanoate (VI) (53.3 g) in toluene (150 ml) was slowly added dropwise, Plus, Reflux reaction about 30h, HPLC monitoring reaction is complete, The reaction solution was cooled to 10 to 15 ° C, filter, The filtrate was concentrated to give 107 g of crude product; With 250mL anhydrous ethanol heated reflux solution, Dropping 80 mL of water, After refluxing for 30 min, Natural cooling to 10 ~ 15 deg C, Insulation stirring 4h, Filtration gave an off-white solid, Drying 90g; And then recrystallized with EA, To obtain 77.4 g of methyl 2- [4- [4- [4- (hydroxydiphenylmethyl) -1-piperidinyl] -butanoyl] phenyl] -2-methylpropionate (VII) as a white solid, Purity 99.5percent Yield 80percent. among them, The molar ratio of methyl 2- (4- (4-chlorobutyryl) phenyl) -2-methylpropanoate (VI), potassium iodide and base is 1: 0.1: 2.23. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(b) Reaction of Methyl-alpha,alpha-dimethylphenyl acetic acid with 4-Chlorobutyryl chlorideMethyl-alpha,alpha-dimethylphenylacetic acid on Fridel-Craft's acylation with 4-chlorobutyryl chloride in presence of anhydrous aluminum chloride in ethylene dichloride produced acylated Methyl-alpha,alpha-dimethylphenyl acetic acid, i.e., ketone intermediate as meta and para- isomers.More particularly, aluminum chloride was taken in dichloroethane and cooled in between about 0 to 2O0C. To the above pre cooled solution, Methyl-alpha,alpha-dimethylphenyl acetic acid was added at low temperature. To the reaction mixture, 4-chlorobutyryl chloride was added between about 0 to 20C. After addition of acid chloride the reaction mixture was stirred for about 8 to 10 hours at the same temperature. After completion of the reaction, mixture was quenched over chilled mixture of potable water and cone, hydrochloric acid followed by stirring the reaction mixture for another 4 hours. The reaction mixture was washed with aqueous solution of sodium bicarbonate and finally with water. Removal of dichloromethane provided Methyl-4-(4-chloro-l-oxobutyryl)-alpha,alpha-dimethylphenyl acetate (Ketone) in about 95 % HPLC purity.EXAMPLE 2Methyl-4-(4-chloro-l-oxobutyryl)- a, a-dimethyl phenyl acetate (Ketone)95 Kg (0.7124 Kmole) of aluminium chloride was taken in 120 Ltr dichloroethane and reaction mixture was cooled to 0 to 2O0C. To it was added ester of example 1, 46 Kg (0.2584 Kmole) through addition flask, maintaining the temperature 0 to 200C. Finally, to the reaction mixture was added 80 Kg (0.5673 Kmoles) of 4-chlorobutyryl chloride through addition flask maintaining the temperature 0 to 200C. After addition of acid chloride stirred the reaction mixture at 0 to 200C for 8 to 10 hours. After completion it was quenched over chilled mixture of potable water and concentrated hydrochloric acid. Then stirred the reaction mixture at 0 to 200C for 4 hours and finally extracted in dichloroethane. It was washed with 10% w/v aqueous solution of sodium bicarbonate and finally with water. Removal of the solvent under vacuum provides thick oily mass of Methyl-4-(4-chloro-l-oxobutyryl)-alpha-alpha-dimethyl phenyl acetate (Ketone). HPLC purity = 95%. Yield = 65 to 70 Kg. | ||
aluminum (III) chloride; In dichloromethane; at 15 - 45℃; for 3h; | Mix AlCl3 (128 g) and methylene chloride (66 mL) and cool with a dry ice/acetone bath to -15 C. Add, by dropwise addition, 4-chlorobutyryl chloride (73.8 g), keeping the temperature below 15 C. Add, by dropwise addition, <strong>[57625-74-8]methyl 2-methyl-2-phenylpropionate</strong> (77.8 g), keeping the temperature below 15 C. After addition is complete, stire the reaction mixture at 22 C. for 10 minutes, then heat to 45 C. for 3 hours. Quench into ice/water (875 g), filter through filter aid, separate the layers and wash the aqueous phase with methylene chloride (50 mL). Combine the organics and evaporate the solvent in vacuo to give 131 g. Decant solids off and place the oil? in a 500 mL 3-neck flask along with methanol (150 mL). Purge with HCl and heat at reflux for 1 hour and allow to stand overnight. Evaporate the solvent in vacuo, dissolve in methylene chloride (250 mL), wash with water (200 mL) and NaHCO3 (300 mL). Evaporate the solvent in vacuo to give a mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (approximately m:p 50:50) (121 g). Place the mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (approximately m:p 50:50) (40.1 g) in a 250 mL, 3-necked flask with a mechanical agitator, N2 blanket and cooling bath. Add methanol (80 mL) at room temperature and cool to -5 C. with and ice/acetone/water bath. Seed with 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and allow to stand at -5 C. for 1 hour. Cool to -10 C. with ice/acetone and allow to stand for 1.5 hours. Cool to -16 C. and hold for 30 minutes. Vacuum filter through a 60 mL sintered glass jacketed filter funnel chilled to -10 C. Wash the filtercake with cold (-50 C.) methanol (30 mL) and cold (-50 C.) n-pentane (30 mL). Dry the filtercake briefly in a stream of nitrogen and vacuum dry (20 C. at 15 mm Hg) to give the mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (approximately m:p 10:90) (10.5 g). Dissolve the mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (approximately m:p 10:90) in methanol (30 mL), cool to 10 C. in an ice/water bath and seed with 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester. Cool to 0 C. and hold for 20 minutes. Vacuum filter, wash and dry as above to give the title compound (5.6 g) as an off-white solid; mp 29.5-30.5 C. | |
aluminum (III) chloride; In dichloromethane; at 15 - 45℃; for 3h; | Mix AlCl3 (128 g) and methylene chloride (66 mL) and cool with a dry ice/acetone bath to -15 C. Add, by dropwise addition, 4-chlorobutyryl chloride (73.8 g), keeping the temperature below 15 C. Add, by dropwise addition, <strong>[57625-74-8]methyl 2-methyl-2-phenylpropionate</strong> (77.8 g), keeping the temperature below 15 C. After addition is complete, stire the reaction mixture at 22 C. for 10 minutes, then heat to 45 C. for 3 hours. Quench into ice/water 875 g), filter through filter aid, separate the layers and wash the aqueous phase with methylene chloride (50 mL). Combine the organics and evaporate the solvent in vacuo to give 131 g. Decant solids off and place the oil in a 500 mL 3-neck flask along with methanol (150 mL). Purge with HCl and heat at reflux for 1 hour and allow to stand overnight. Evaporate the solvent in vacuo, dissolve in methylene chloride (250 mL), wash with water (200 mL) and NaHCO3 (300 mL). Evaporate the solvent in vacuo to give a mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (121 g) (approximately 50:50 m:p). Place the mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (approximately 50:50 m:p) (40.1 g) in a 250 mL, 3-necked flask with a mechanical agitator, N2 blanket and cooling bath. Add methanol (80 mL) at room temperature and cool to -5 C. with and ice/acetone/water bath. Seed with 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and allow to stand at -5 C. for 1 hour. Cool to -10 C. with ice/acetone and allow to stand for 1.5 hours. Cool to -16 C. and hold for 30 minutes. Vacuum filter through a 60 mL sintered glass jacketed filter funnel chilled to -10 C. Wash the filtercake with cold (-50 C.) methanol (30 mL) and cold (-50 C.) n-pentane (30 mL). Dry the filtercake briefly in a stream of nitrogen and vacuum dry (20 C. at 15 mm Hg) to give the mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (approximately 10:90 m:p) (10.5 g). To the methanol solution of the mixture of 2-[4-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester and 2-[3-(4-chloro-butyrl)-phenyl]-2-methyl-proprionic acid, methyl ester (approximately 50:50 m:p) (approximately 70:30 m:p) from crystallization (i.e. mother liquor), slowly add 1 to 1.2 euivalents of 25% NaOMe/MeOH solution. Agitate for approximately 30 minutes at 25 C. Neutralize the excess NaOMe with excess carbon dioxide. Add water (300 mL) per mole of subtrate, evaporate the methanol by vacuum distiallation and decant the aqueous layer to give a mixture of 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid, methyl ester and 2-(3-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid, methyl ester (approximately 70:30 m:p). Distill the mixture of 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid, methyl ester and 2-(3-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid, methyl ester (approximately 70:30 m:p) at 0.5 mm Hg and discard a light fraction boiling at 25-130 C. (pot temp-105-165 C.). Continue distilling the oil at 0.5 mm Hg and collect a second fraction boiling at 130-150 C. (pot temperature 165-190) to give the mixture of 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid, methyl ester and 2-(3-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid, methyl ester (approximately 70:30 m:p) Pack a {fraction (31/32)} in. I.D. vacuum jacked and silvered column with 53 inches of 1 in. diameter, 316 stainless steel packing. For high temperature distillation, the column is fitted with an adiabatic jacket composed of an inner layer of 1 in. fiber glass wrapped with heat tape in an upper and lower zone and finally covered with 2 in. fiber glass insulation. The upper zone is heated at 135 C. and the lower z |
Tags: 154477-54-0 synthesis path| 154477-54-0 SDS| 154477-54-0 COA| 154477-54-0 purity| 154477-54-0 application| 154477-54-0 NMR| 154477-54-0 COA| 154477-54-0 structure
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