1,1,1-trichloro-2-methylpropan-2-ol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cold (0° C.), well stirred suspension of NaOH (1.6 g, 40 mmoles) and 4-bromo-3,5-dimethylpyrazole (1.75 g, 10 mmoles) in acetone (100 mL), was added 2-(trichloromethyl)-propan-2-ol (3.54 g, 20 mmoles) portion-wise over 1 hour. The mixture was allowed to warm to room temperature overnight. The solvent was evaporated under reduced pressure. The residue was dissolved in water (100 mL) and washed with ether (50 mL). The aqueous phase was separated and acidified with conc. HCl to pH=3. The mixture was extracted with CH2Cl2 (3×50 mL) and the combined organics dried over Na2SO4. A colorless oil was obtained after the removal of the solvent under reduced pressure. MS(DCI+) m/z 263 (M+H)+. The solvent was evaporated under reduced pressure The residue was dissolved in water (100 mL) washed with ether (50 mL) The aqueous phase was separated The mixture was extracted with CH2Cl2 (3×50 mL) the combined organics dried over Na2SO4 A colorless oil was obtained after the removal of the solvent under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon atmosphere, 24 mg of triturated sodium hydroxide was added to 2 ml of a solution of 100 mg of 4-(6-acetylthiohexyl)-5-methyl-2-(p-tolyl)oxazole in acetone, and stirred for 2 hours at room temperature. To the reaction solution, 20 μl of water was added, followed by addition of 113 mg of 1,1,1-trichloro-2-methyl-2-propanol.0.5 hydride (chloretone), and then 96.5 mg of triturated sodium hydroxide in tree portions at 30 minutes intervals. The mixture was stirred for additional 18 hours at room temperature. The reaction solution was concentrated. The residue was, after addition of water, extracted with diethyl ether. The organic layers were combined, washed with water, and the washings was acidified with 1 N hydrochloric acid and extracted with ethyl acetate. The organic layers were combined, washed with water and brine sequentially, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Wakogel® C-200, chloroform:methanol=100:1) and the resulting crystals were washed with n-hexane to provide 28.0 mg of the objective compound as pale yellow crystals. The mixture was stirred for additional 18 hours at room temperature The reaction solution was concentrated after addition of water extracted with diethyl ether washed with water extracted with ethyl acetate washed with water and brine sequentially dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (Wakogel® C-200, chloroform:methanol=100:1) the resulting crystals were washed with n-hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon atmosphere, 24 mg of triturated sodium hydroxide was added to 2 ml of a solution of 100 mg of 4-(6-acetylthiohexyl)-5-methyl-2-(p-tolyl)oxazole in acetone, and stirred for 2 hours at room temperature. To the reaction solution, 20 μl of water was added, followed by addition of 113 mg of 1,1,1-trichloro-2-methyl-2-propanol.0.5 hydride (chloretone), and then 96.5 mg of triturated sodium hydroxide in tree portions at 30 minutes intervals. The mixture was stirred for additional 18 hours at room temperature. The reaction solution was concentrated. The residue was, after addition of water, extracted with diethyl ether. The organic layers were combined, washed with water, and the washings was acidified with 1 N hydrochloric acid and extracted with ethyl acetate. The organic layers were combined, washed with water and brine sequentially, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Wakogel® C-200, chloroform:methanol=100:1) and the resulting crystals were washed with n-hexane to provide 28.0 mg of the objective compound as pale yellow crystals. The mixture was stirred for additional 18 hours at room temperature The reaction solution was concentrated after addition of water extracted with diethyl ether washed with water extracted with ethyl acetate washed with water and brine sequentially dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (Wakogel® C-200, chloroform:methanol=100:1) the resulting crystals were washed with n-hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(trifluoromethyl)phenol (3.20 g, 20.0 mmol) in acetone (20 mL) was added with 1,1,1-trichloro-2-methyl-2-propanol 0.5 hydrate (7.82 g, 40.0 mmol) and sodium hydrate (3.20 g, 80.0 mmol) at 0° C., and the resultant was stirred at room temperature for 20 hours. The reaction solution was concentrated in vacuo, added with water, and washed with diethylether. The aqueous layer was neutralized with concentrated hydrochloric acid, and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, concentrated in vacuo, and 2-methyl-2-[2-(trifluoromethyl)phenoxy]propionic acid (1.35 g, 27.2%) was obtained as a white amorphous solid. The reaction solution was concentrated in vacuo added with water washed with diethylether extracted with chloroform The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Amino-2-fluoro-benzoic acid (0.2 g, 1.29 mmol) and 1,1,1-trichloro-2-methyl-propan-2-ol (0.593 g, 3.35 mmol) were dissolved in anhydrous acetone and the solution was cooled at 0° C. Powdered sodium hydroxide (0.2 g, 5.01 mmol) was added portion-wise after which the reaction mixture was warmed to and stirred at room temperature for 12 h. Volatiles were removed under reduced pressure and the residue was acidified with 1M aqueous HCl. The crude product obtained was purified by reverse phase HPLC to obtain 4-(1-carboxy-1-methyl-ethylamino)-2-fluoro-benzoic acid. was warmed to and Volatiles were removed under reduced pressure The crude product obtained was purified by reverse phase HPLC

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Amino-2-fluoro-benzoic acid (0.2 g, 1.29 mmol) and 1,1,1-trichloro-2-methyl-propan-2-ol (0.593 g, 3.35 mmol) were dissolved in anhydrous acetone and the solution was cooled at 0° C. Powdered sodium hydroxide (0.2 g, 5.01 mmol) was added portion-wise after which the reaction mixture was warmed to and stirred at room temperature for 12 h. Volatiles were removed under reduced pressure and the residue was acidified with 1M aqueous HCl. The crude product obtained was purified by reverse phase HPLC to obtain 4-(1-carboxy-1-methyl-ethylamino)-2-fluoro-benzoic acid. was warmed to and Volatiles were removed under reduced pressure The crude product obtained was purified by reverse phase HPLC

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An analysis of the crude reaction solution by gas chromatography revealed that the conversion of 1,1,1-trichloro-2-methyl-2-propanol was 67.7% and the yield of methyl 2-chloro-2-methylpropanoate was 36.5%. As to other products, it was obtained (1,1,1-trichloro-2-methyl-2-propyl) methacrylate in a 10.5% yield, and (1,1,1-trichloro-2-methyl-2-propyl) 2-chloro-2-methylpropanoate in a 13.5% yield. The crude reaction solution obtained was distilled under a reduced pressure, thereby obtaining methyl 2-chloro-2-methylpropanoate at a purity of 85%. An analysis of the crude reaction solution by gas chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An analysis of the crude reaction solution by gas chromatography revealed that the conversion of 1,1,1-trichloro-2-methyl-2-propanol was 67.7% and the yield of methyl 2-chloro-2-methylpropanoate was 36.5%. As to other products, it was obtained (1,1,1-trichloro-2-methyl-2-propyl) methacrylate in a 10.5% yield, and (1,1,1-trichloro-2-methyl-2-propyl) 2-chloro-2-methylpropanoate in a 13.5% yield. The crude reaction solution obtained was distilled under a reduced pressure, thereby obtaining methyl 2-chloro-2-methylpropanoate at a purity of 85%. An analysis of the crude reaction solution by gas chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The analysis of the crude reaction solution by gas chromatography revealed that the conversion of 1,1,1-trichloro-2-methyl-2-propanol was 70.0% and the yield of methyl 2-chloro-2-methylpropanoate was 23.9%. As to other products, it was obtained methyl methacrylate in a 0.7% yield, methacrylic acid in a 0.2% yield, (1,1,1-trichloro-2-methyl-2-propyl) methacrylate in a 7.8% yield, and (1,1,1-trichloro-2-methyl-2-propyl) 2-chloro-2-methylpropanoate in a 12.9% yield. The analysis of the crude reaction solution by gas chromatography

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 2.83 g of the crude reaction solution obtained was added 0.11 g of methanol, followed by heating at 60° C. for 4 hours. Then, it was found out by gas chromatography analysis that the conversion of the 1,1,1-trichloro-2-methyl-2-propanol was 86.0% and the yield of methyl 2-chloro-2-methylpropanoate was 10.2%. As to other products, it was obtained methyl methacrylate in a 0.2% yield, methacrylic acid in a 8.7% yield, (1,1,1-trichloro-2-methyl-2-propyl) methacrylate in a 13.1% yield, and (1,1,1-trichloro-2-methyl-2-propyl) 2-chloro-2-methylpropanoate in a 22.8% yield. To 2.83 g of the crude reaction solution obtained

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: As a result of the analysis, it was found out that, as mentioned below, the conversion of 1,1,1-trichloro-2-methyl-2-propanol was 85.4% and the yield of 2-chloro-2-methylpropanoic acid was 54.4%. As to other products, it was obtained methacrylic acid in a 2.3% yield, (1,1,1-trichloro-2-methyl-2-propyl) methacrylate in a 22.7% yield, and (1,1,1-trichloro-2-methyl-2-propyl) 2-chloro-2-methylpropanoate in a 7.8% yield. As a result of the analysis, it

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: As a result of the analysis, it was found out that, as mentioned below, the conversion of 1,1,1-trichloro-2-methyl-2-propanol was 85.4% and the yield of 2-chloro-2-methylpropanoic acid was 54.4%. As to other products, it was obtained methacrylic acid in a 2.3% yield, (1,1,1-trichloro-2-methyl-2-propyl) methacrylate in a 22.7% yield, and (1,1,1-trichloro-2-methyl-2-propyl) 2-chloro-2-methylpropanoate in a 7.8% yield. As a result of the analysis, it