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With sulfuric acid; at 20℃; for 12h;Heating / reflux;
Methanol (2.5 LTR), 2,2-dimethyl-2-phenyl-acetic acid (Intermediate 1) (0.5 kg), and conc. sulphuric acid (50 ml) were charged to a reactor at room temperature. The temperature was raised to reflux and maintained for 12 hours. The pH was adjusted to 7-8 using aqueous ammonia and the methanol concentrated completely. The reaction mass was quenched in water (1 LTR) and extracted with MDC (750 ml). The MDC layer was dried over sodium sulphate and concentrated to obtain 500 gms of the title compound as an oil having 98% purity
With sulfuric acid; at 25 - 45℃; for 4h;Heating / reflux;
(a) Reaction of alpha,alpha-Dimethyl phenyl acetic acid and methanol alpha,alpha-Dimethylphenyl acetic acid was reacted with methanol in presence of cone, sulfuric acid between about 25 to 45C. Reaction mixture was refluxed for about 4 hours. Methanol was distilled off after the said time to give thick oily slurry of Methyl-alpha,alpha-dimethylphenyl acetic acid. Water was added to the pre-cooled reaction mixture and extracted with chloroform EPO <DP n="8"/>followed by washing with aqueous sodium bicarbonate solution and finally with potable water. Removal of chloroform under reduced pressure yielded title compound as oily mass in about 98 % HPLC purity.EXAMPLE 1Methyl- a, a-Dimethyl phenyl acetate (ester)51 Kg (0.3109 Kmole) of alpha,alpha-Dimethyl acetic acid was dissolved in 100 to 150 Ltr methanol and to it was added concentrated sulfuric acid, 6 to 9 Kg maintaining temperature 25 to 450C. After complete addition of sulfuric acid reaction mixture was refluxed for 4 hours. After completion of the reaction methanol was distilled off under vacuum to obtain thick slurry which was cooled to room temperature and to it was added water. Reaction mixture was then extracted with chloroform and washed with 10% w/v sodium bicarbonate aqueous solution. Finally, chloroform layer was washed with potable water. On removal of chloroform under vacuum, Methyl-alpha,alpha-Dimethyl phenyl acetate as oily mass was obtained. HPLC Purity = 98%. Yield = 40 to 50 Kg
1 g
With methanesulfonic acid; for 2h;Sealed tube; Reflux;
A 100 mL sealed tube was charged with intermediate 39b (1.6 g, 9.7 mmol) and methanol (10 mL). To the above stirred solution CH3SO3H (1 .6 mL) was added drop wise and refluxed for 2 h. The reaction mixture concentrated and was diluted with ice- water and neutralized with NaHCO3, extracted with ethyl acetate, washed with water and dried. The product was obtained by concentrating under vacuo, which was further purified by combiflash to yield the title compound (1 .0 g) as a colourless liquid.H NMR: (ODd3, 300MHz) 6 7.25-7.27(d, 4H) 7.17-7.20 (m, 1H), 3.58 (5, 3H),1 .51 (5, 6H).
2 g
With sulfuric acid; at 0℃;Reflux;
To a stirred solution of 2-methyi-2-phenyipropanoic acid (2 g, 12.18 mmol) in methanol (30m1) at 0 was added drop wise solution of H2S04 (2 ml, 37.5 mmol), The reaction mixture was heated torefiux for overnight. After completion of reaction, methanol was evaporated under reduced pressure and the residue was diluted with dichioromethane. The organic portion was washed with saturatedsodium bicarbonate solution, brine and evaporated under reduced pressure to give methyl 2-methyl-2-phenyipropanoate (2 g) as oil.
With water; sodium hydroxide; In 1,4-dioxane; for 24h;
Methyl 2-methyl-2-phenylpropanoate (0.840 g, 4.71 mmol) was dissolved in 5 mL of l,4-dioxane and 10 mL of 1.0 M NaOH (10.0 mmol, 2.1 equiv) was added. The mixture was heated at 95 C for 24 h. 20 mL of 1.0 M HC1 was added and the mixture was extracted with dichloromethane (3 x 20 mL). Combined organic fractions were washed with brine (30 mL), filtered through cotton and concentrated under reduced pressure to yield a crude mixture which was purified by flash chromatography (hexanes/ethyl acetate), 0.758 g of 2-methyl-2-phenylpropanoic acid (4.62 mmol, 98%).
89 g
With water; sodium hydroxide; In methanol; at 10℃; for 3h;Reflux;
Example-l: Preparation of 2-methyl-2-phenylpropanoic acid (FormuIa-3) Methyl 2-methyl-2-phenylpropanoate compound of formula-2 (100 gm) and methanol (500 ml) were added to a pre-cooled mixture of sodium hydroxide (45 gm) and water (500 ml) at 10-15C. Heated the reaction mixture to reflux temperature and stirred for 3 hrs at the same temperature. Distilled off the solvent completely from the reaction mixture under reduced pressure and cooled the reaction mixture to 25-30C. Water was added to the reaction mixture and cooled to 5-10C. Acidified the reaction mixture using dil.HCl solution at 5-10C. Raised the temperature of the reaction mixture to 25-30C and stirred for 30 rhin at the same temperature. Filtered the solid, washed with water and dried the material to get the title compound. Yield: 89.0 gm.
With water; sodium hydroxide; In methanol; at 65℃;
General procedure: The ester II was added to a mixture of NaOH (2.0 M, 8 mL) and methanol (10 mL)and stirred overnight at 65 C. After removal of methanol in vacuo, the residue wasdiluted with water and extracted with EtOAc (10 mL × 3). Then the pH value of thewater layer was adjusted to 2.0 with HCl (2.0 M) and extracted with EtOAc (30 mL ×3). The combined organic phases were evaporated in vacuo to give the crudecarboxylic acid III, which was used directly for the next step without furtherpurification.
EXAMPLE 6 Following the procedure of Example 1, the enol ether of isobutyrophenone of the formula STR10 is reacted with thallium (III) acetate to give methyl 2-methyl-2-phenylpropionate. This ester is hydrolyzed to yield 2-methyl-2-phenylpropionic acid.
EXAMPLE 6 Following the procedure of Example 1, the enol ether of isobutyrophenone of the formula STR3 is reacted with thallium (III) aceetate to give methyl 2-methyl-2-phenylpropionate. This ester is hydrolyzed to yield 2-methyl-2-phenylpropionic acid.
7
[ 826-55-1 ]
[ 74-88-4 ]
[ 57625-74-8 ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 20℃; for 40h;
2-Methyl-2-phenyl-propionic acid methyl ester: 9.00 g (55 mmol) 2-methyl-2-phenyl-propionic acid was dissolved in 90 ml N,N-dimethylformamide, 11.51 g (2.5 eq.) of sodium hydrogencarbonate was added followed by 6.89 mL (15.72 g 2 eq.) of methyl iodide. The mixture was stirred at rt for 40 hours, then poured into ice water, the pH was adjusted to 3.0 with aq. HCl (1N) and the mixture extracted 3 times with ether; the organic phases were washed with water, dried over MgSO4, filtered and evaporated to give 7.34 g of the crude title compound as yellow oil. MS: 178.1 (M+).
A 100 mL sealed tube was charged with intermediate 39b (1.6 g, 9.7 mmol) and methanol (10 mL). To the above stirred solution, CH3SO3H (1.6 mL) was added drop wise and refluxed for 2 h. The reaction mixture concentrated and was diluted with ice-water and neutralized with NaHCO3, extracted with ethyl acetate, washed withwater and dried. The product was obtained by concentrating under vacuo, which wasfurther purified by combiflash to yield the title compound (1 .0 g) as a colourless liquid.1H NMR: (ODd3, 300MHz) 6 7.25-7.27(d, 4H) 7.17-7.20 (m, 1H), 3.58 (5, 3H),1 .51(s, 6H).
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