4-chloro-2-(trifluoromethyl)phenol

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

実験手順: To a 300 ml, 3-necked flask fitted with a stirrer, condenser, thermometer and drying tube is added dimethylsulfoxide (100 ml), tert-butanol (20 ml), powdered potassium hydroxide (KOH) pellets (85%, 30 g) and 2,5-dichlorobenzotrifluoride (21.5 g, 0.10 mole). The reaction mixture is warmed to 71°-73° C. for 60 hours, then additional KOH (10 g) is added and heating is continued at 73°-75° C. for 24 hours. The reaction mixture is cooled and the solvent partially removed by distillation at 0.9 mm, bp 55° C.). The cooled pot residue is then poured into ice water (1000 g) which had been preacidified to pH 1 with conc. HCl (50 ml). The aqueous mixture is extracted with carbon tetrachloride (CCl4), the CCl4 layer decanted and dried and the solvent removed under vacuum to afford 10.8 g of 4-chloro-2-trifluoromethylphenol, which is sublimed to afford pure product, mp 81° -81.5° C. Elemental Anal. Calcd for C7H4ClF3O: C, 42.75; H, 2.06; Cl, 18.04: Found: C, 42.54; H, 2.36; Cl, 18.16. ##STR10## To a 300 ml, 3-necked flask fitted with a stirrer, condenser thermometer and drying tube The reaction mixture is warmed to 71°-73° C. for 60 hours heating The reaction mixture is cooled the solvent partially removed by distillation at 0.9 mm, bp 55° C.) The cooled pot residue is then poured into ice water (1000 g) which The aqueous mixture is extracted with carbon tetrachloride (CCl4) the CCl4 layer decanted dried the solvent removed under vacuum

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

実験手順: To a 300 ml, 3-necked flask fitted with a stirrer, condenser, thermometer and drying tube is added dimethylsulfoxide (100 ml), tert-butanol (20 ml), powdered potassium hydroxide (KOH) pellets (85%, 30 g) and 2,5-dichlorobenzotrifluoride (21.5 g, 0.10 mole). The reaction mixture is warmed to 71°-73° C. for 60 hours, then additional KOH (10 g) is added and heating is continued at 73°-75° C. for 24 hours. The reaction mixture is cooled and the solvent partially removed by distillation at 0.9 mm, bp 55° C.). The cooled pot residue is then poured into ice water (1000 g) which had been preacidified to pH 1 with conc. HCl (50 ml). The aqueous mixture is extracted with carbon tetrachloride (CCl4), the CCl4 layer decanted and dried and the solvent removed under vacuum to afford 10.8 g of 4-chloro-2-trifluoromethylphenol, which is sublimed to afford pure product, mp 81° -81.5° C. Elemental Anal. Calcd for C7H4ClF3O: C, 42.75; H, 2.06; Cl, 18.04: Found: C, 42.54; H, 2.36; Cl, 18.16. ##STR10## To a 300 ml, 3-necked flask fitted with a stirrer, condenser thermometer and drying tube The reaction mixture is warmed to 71°-73° C. for 60 hours heating The reaction mixture is cooled the solvent partially removed by distillation at 0.9 mm, bp 55° C.) The cooled pot residue is then poured into ice water (1000 g) which The aqueous mixture is extracted with carbon tetrachloride (CCl4) the CCl4 layer decanted dried the solvent removed under vacuum

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

実験手順: To a 300 ml, 3-necked flask fitted with a stirrer, condenser, thermometer and drying tube is added dimethylsulfoxide (100 ml), tert-butanol (20 ml), powdered potassium hydroxide (KOH) pellets (85%, 30 g) and 2,5-dichlorobenzotrifluoride (21.5 g, 0.10 mole). The reaction mixture is warmed to 71°-73° C. for 60 hours, then additional KOH (10 g) is added and heating is continued at 73°-75° C. for 24 hours. The reaction mixture is cooled and the solvent partially removed by distillation at 0.9 mm, bp 55° C.). The cooled pot residue is then poured into ice water (1000 g) which had been preacidified to pH 1 with conc. HCl (50 ml). The aqueous mixture is extracted with carbon tetrachloride (CCl4), the CCl4 layer decanted and dried and the solvent removed under vacuum to afford 10.8 g of 4-chloro-2-trifluoromethylphenol, which is sublimed to afford pure product, mp 81°-81.5° C. Elemental Anal. Calcd for C7H4ClF3O: C, 42.75; H, 2.06; Cl, 18.04: Found: C, 42.54; H, 2.36; Cl, 18.16. ##STR14## To a 300 ml, 3-necked flask fitted with a stirrer, condenser thermometer and drying tube The reaction mixture is warmed to 71°-73° C. for 60 hours heating The reaction mixture is cooled the solvent partially removed by distillation at 0.9 mm, bp 55° C.) The cooled pot residue is then poured into ice water (1000 g) which The aqueous mixture is extracted with carbon tetrachloride (CCl4) the CCl4 layer decanted dried the solvent removed under vacuum

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

実験手順: To a 300 ml, 3-necked flask fitted with a stirrer, condenser, thermometer and drying tube is added dimethylsulfoxide (100 ml), tert-butanol (20 ml), powdered potassium hydroxide (KOH) pellets (85%, 30 g) and 2,5-dichlorobenzotrifluoride (21.5 g, 0.10 mole). The reaction mixture is warmed to 71°-73° C. for 60 hours, then additional KOH (10 g) is added and heating is continued at 73°-75° C. for 24 hours. The reaction mixture is cooled and the solvent partially removed by distillation at 0.9 mm, bp 55° C.). The cooled pot residue is then poured into ice water (1000 g) which had been preacidified to pH 1 with conc. HCl (50 ml). The aqueous mixture is extracted with carbon tetrachloride (CCl4), the CCl4 layer decanted and dried and the solvent removed under vacuum to afford 10.8 g of 4-chloro-2-trifluoromethylphenol, which is sublimed to afford pure product, mp 81°-81.5° C. Elemental Anal. Calcd for C7H4ClF3O: C, 42.75; H, 2.06; Cl, 18.04: Found: C, 42.54; H, 2.36; Cl, 18.16. ##STR14## To a 300 ml, 3-necked flask fitted with a stirrer, condenser thermometer and drying tube The reaction mixture is warmed to 71°-73° C. for 60 hours heating The reaction mixture is cooled the solvent partially removed by distillation at 0.9 mm, bp 55° C.) The cooled pot residue is then poured into ice water (1000 g) which The aqueous mixture is extracted with carbon tetrachloride (CCl4) the CCl4 layer decanted dried the solvent removed under vacuum

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

実験手順: A three-neck round bottom flask affixed with an overhead stirrer was charged with 4-chloro-2-(trifluoromethyl)phenol (prepared according methods described in U.S. Pat. No. 4,262,152), (5.0 g, 127 mmol, 1.0 eq) and dissolved in chloroform (3.3 mL) and acetone (8.4 mL). NaOH pellets (4.2 g, 104 mmol, 3.75 eq) were added in 2 portions and the mixture was stirred vigorously for 40 min. The resulting slurry was acidified to pH 2 with 3N HCl and extracted with EtOAc. The organic extracts were treated with satd. aq. sodium bicarbonate, and the basic layer was acidified to pH 4 with conc. HCl and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate and concentrated to afford 2.7 g (37%) of 2-(4-chloro-2-(trifluoromethyl)phenoxy)-2-methylpropanoic acid as a light brown crystalline solid. 1H NMR (400 MHz, CDCl3): δ 7.57 (d, J=2.6 Hz, 1H), 7.40 (dd, J=8.9, 2.6 Hz, 1H), 6.91 (d, J=8.9 Hz, 1H), 1.67 (s, 6H). LCMS (0-99% MeCN/water, 5 min, negative ion), Tret=2.99 min, [M−H]−=281.3 observed. A three-neck round bottom flask affixed with an overhead stirrer prepared were added in 2 portions extracted with EtOAc The organic extracts were treated with satd extracted with EtOAc The organic layer was washed with brine dried over sodium sulfate concentrated

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

実験手順: To a 300 ml, 3-necked flask fitted with a stirrer, condenser, thermometer and drying tube is added dimethylsulfoxide (100 ml), tert-butanol (20 ml), powdered potassium hydroxide (KOH) pellets (85%, 30 g) and 2,5-dichlorobenzotrifluoride (21.5 g, 0.10 mole). The reaction mixture is warmed to 71°-73° C. for 60 hours, then additional KOH (10 g) is added and heating is continued at 73°-75° C. for 24 hours. The reaction mixture is cooled and the solvent partially removed by distillation at 0.9 mm, bp 55° C.). The cooled pot residue is then poured into ice water (1000 g) which had been preacidified to pH 1 with conc. HCl (50 ml). The aqueous mixture is extracted with carbon tetrachloride (CCl4), the CCl4 layer decanted and dried and the solvent removed under vacuum to afford 10.8 g of 4-chloro-2-trifluoromethylphenol, which is sublimed to afford pure product, mp 81° -81.5° C. Elemental Anal. Calcd for C7H4ClF3O: C, 42.75; H, 2.06; Cl, 18.04: Found: C, 42.54; H, 2.36; Cl, 18.16. ##STR10## To a 300 ml, 3-necked flask fitted with a stirrer, condenser thermometer and drying tube The reaction mixture is warmed to 71°-73° C. for 60 hours heating The reaction mixture is cooled the solvent partially removed by distillation at 0.9 mm, bp 55° C.) The cooled pot residue is then poured into ice water (1000 g) which The aqueous mixture is extracted with carbon tetrachloride (CCl4) the CCl4 layer decanted dried the solvent removed under vacuum

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

実験手順: To a 300 ml, 3-necked flask fitted with a stirrer, condenser, thermometer and drying tube is added dimethylsulfoxide (100 ml), tert-butanol (20 ml), powdered potassium hydroxide (KOH) pellets (85%, 30 g) and 2,5-dichlorobenzotrifluoride (21.5 g, 0.10 mole). The reaction mixture is warmed to 71°-73° C. for 60 hours, then additional KOH (10 g) is added and heating is continued at 73°-75° C. for 24 hours. The reaction mixture is cooled and the solvent partially removed by distillation at 0.9 mm, bp 55° C.). The cooled pot residue is then poured into ice water (1000 g) which had been preacidified to pH 1 with conc. HCl (50 ml). The aqueous mixture is extracted with carbon tetrachloride (CCl4), the CCl4 layer decanted and dried and the solvent removed under vacuum to afford 10.8 g of 4-chloro-2-trifluoromethylphenol, which is sublimed to afford pure product, mp 81°-81.5° C. Elemental Anal. Calcd for C7H4ClF3O: C, 42.75; H, 2.06; Cl, 18.04: Found: C, 42.54; H, 2.36; Cl, 18.16. ##STR14## To a 300 ml, 3-necked flask fitted with a stirrer, condenser thermometer and drying tube The reaction mixture is warmed to 71°-73° C. for 60 hours heating The reaction mixture is cooled the solvent partially removed by distillation at 0.9 mm, bp 55° C.) The cooled pot residue is then poured into ice water (1000 g) which The aqueous mixture is extracted with carbon tetrachloride (CCl4) the CCl4 layer decanted dried the solvent removed under vacuum