tert-butyl 2-(4-methylphenyl)acetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33.5 g (0.3 mol) of potassium tert-butylate are initially introduced into 100 ml of anhydrous DMF at 0° C., and 51.6 g (0.25 mol) of tert-butyl 4methylphenyl-acetate in 250 ml of anhydrous DMF are added dropwise. The mixture is stirred at 0° C. for 30 minutes, 32.2 ml (0.3 mol) of cyclopentyl bromide in 150 ml of anhydrous DMF are added dropwise at 5-15° C. and the mixture is stirred at 25° C. for 20 hours. After concentration, the residue is partitioned between water and diethyl ether and the ether phase is dried over sodium sulphate and concentrated. The product crystallizes out. the mixture is stirred at 25° C. for 20 hours After concentration the residue is partitioned between water and diethyl ether the ether phase is dried over sodium sulphate concentrated The product crystallizes out

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 19.58 g (174.5 mmol) of potassium tert-butoxide were initially charged in 200 ml of DMF, the mixture was cooled to 0° C., 30 g (145.4 mmol) of tert-butyl (4-methylphenyl)acetate, dissolved in 50 ml of DMF, were added slowly and the mixture was then stirred at 0° C. for 30 min. 18.95 ml (174.5 mmol) of 2-bromobutane were then slowly added drowise, and the solution was stirred at 0° C. for 4 h. 200 ml of water and 200 ml of diethyl ether were then added to the reaction solution. The aqueous phase was extracted twice with diethyl ether. The combined organic phases were dried over magnesium sulfate. After filtration, the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave 15.5 g (59.1 mmol, 40.6% of theory) of a colorless liquid. were added slowly the solution was stirred at 0° C. for 4 h The aqueous phase was extracted twice with diethyl ether The combined organic phases were dried over magnesium sulfate After filtration the solvent was removed under reduced pressure The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With exclusion of oxygen, 0.88 ml (6.3 mmol) of diisopropylamine were initially charged in 20 ml of THF, the mixture was cooled to −78° C. and 2.52 ml (6.3 mmol) of a 2.5 M solution of n-butyl-lithium in hexane were added slowly. The reaction solution was then warmed to −10° C. and stirred at this temperature for 10 min. The reaction solution was then once more cooled to −78° C., and 1 g (4.85 mmol) of tert-butyl (4-methylphenyl)acetate, dissolved in 10 ml of THF, was added slowly. The reaction solution was then slowly warmed to −30° C. and then once more cooled to −78° C. Once this temperature had been reached, 0.62 ml (5.82 mmol) of 3-bromo-1,1,1-trifluoropropane was slowly added dropwise. After the addition had ended, the solution was slowly warmed to room temperature and stirred overnight. The reaction was checked by TLC (mobile phase cyclohexane/ethyl acetate 10:1), after which saturated ammonium chloride solution was added and the mixture was taken up in ethyl acetate. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate. After filtration, the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 10:1). This gave 542 mg (1.79 mmol, 37% of theory) of a yellowish oil. The reaction solution was then warmed to −10° C. The reaction solution was then once more cooled to −78° C. was added slowly The reaction solution was then slowly warmed to −30° C. once more cooled to −78° C After the addition the solution was slowly warmed to room temperature stirred overnight The aqueous phase was extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate After filtration the solvent was removed under reduced pressure The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 10:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33.5 g (0.3 mol of potassium tert-butoxide are initially introduced into 100 ml of anhydrous DMF at 0° C., and 51.6 g (0.25 mol) of the compound from Example XX in 250 ml of anhydrous DMF are added dropwise. The mixture is stirred at 0° C. for 30 min and 32.2 ml (0.3 mol) of cyclopentyl bromide in 150 ml of anhydrous DMF are added dropwise at 5-15° C. and the mixture is stirred at 25° C. for 20 h. After concentrating, the residue is partitioned between water and diethyl ether, and the ether phase is dried over sodium sulphate and concentrated. The product crystallizes out. the mixture is stirred at 25° C. for 20 h After concentrating the residue is partitioned between water and diethyl ether the ether phase is dried over sodium sulphate concentrated The product crystallizes out

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 450 g (3 mol) of 4-methylphenyl-acetic acid (Aldrich), 1.13 l (12 mol) of tert-butanol and 90 g (0.74 mol) of 4-(N,N-diethylamino)pyridine are dissolved in 2 l of dichloromethane. After addition of 680 g (3.3 mol of dicyclohexylcarbodiimide, dissolved in 400 ml of dichloromethane, the mixture is stirred at 25° C. for 20 h, the precipitated urea is filtered off with suction and washed with 200 ml of dichloromethane, and the organic phase is washed twice each with 500 ml of 2 M hydrochloric acid and water. The organic phase is concentrated and distilled. the precipitated urea is filtered off with suction washed with 200 ml of dichloromethane the organic phase is washed twice each with 500 ml of 2 M hydrochloric acid and water The organic phase is concentrated distilled

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33.5 g (0.3 mol of potassium tert-butoxide are initially introduced into 100 ml of anhydrous DMF at 0° C., and 51.6 g (0.25 mol) of the compound from Example XX in 250 ml of anhydrous DMF are added dropwise. The mixture is stirred at 0° C. for 30 min and 32.2 ml (0.3 mol) of cyclopentyl bromide in 150 ml of anhydrous DMF are added dropwise at 5-15° C. and the mixture is stirred at 25° C. for 20 h. After concentrating, the residue is partitioned between water and diethyl ether, and the ether phase is dried over sodium sulphate and concentrated. The product crystallizes out. the mixture is stirred at 25° C. for 20 h After concentrating the residue is partitioned between water and diethyl ether the ether phase is dried over sodium sulphate concentrated The product crystallizes out

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 450 g (3 mol) of 4-methylphenyl-acetic acid (Aldrich), 1.13 l (12 mol) of tert-butanol and 90 g (0.74 mol) of 4- ,(N,N- dimethylamino)pyridine are dissolved in 2 l of dichioromethane. After addition of 680 g (3.3 mol of dicyclohexylcarbodiimide, dissolved in 400 ml of dichloromethane, the mixture is stirred at 25° C. for 20 h, the precipitated urea is filtered off with suction and washed with 200 ml of dichloromethane, and the organic phase is washed twice each with 500 ml of 2 M hydrochloric acid and water. The organic phase is concentrated and distilled. the precipitated urea is filtered off with suction washed with 200 ml of dichloromethane the organic phase is washed twice each with 500 ml of 2 M hydrochloric acid and water The organic phase is concentrated distilled

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 4.4 ml (31.5 mmol) of diisopropylamine were initially charged in 50 ml of THF, the mixture was cooled to −30° C. and 13.7 ml (31.5 mmol) of a 2.3 M solution of n-butyllithium in hexane were added slowly. The reaction solution was then warmed to −20° C., 5 g (24.3 mmol) of tert-butyl(4-methylphenyl)acetate, dissolved in 30 ml of THF, were added slowly, and the mixture was stirred at this temperature for 2 hours. The reaction solution was then cooled to −78° C., and 2.2 ml (25.7 mmol) of 2-cyclopenten-1-one, dissolved in 20 ml of THF, were added slowly. After the addition had ended, the solution was stirred at this temperature for another hour. After TLC check (mobile phase cyclohexane/ethyl acetate 9:1), saturated ammonium chloride solution was added and the mixture was taken up in ethyl acetate. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate. After filtration, the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1). This gave 3020 mg (10.47 mmol, 43% of theory) of the title compound as a colorless oil. The reaction solution was then warmed to −20° C. were added slowly The reaction solution was then cooled to −78° C. were added slowly After the addition the solution was stirred at this temperature for another hour The aqueous phase was extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate After filtration the solvent was removed under reduced pressure The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under exclusion of oxygen, 0.44 ml (3.2 mmol) of diisopropylamine was initially charged in 4 ml of THF, the mixture was cooled to −78° C. and 1.28 ml (3.2 mmol) of a 2.5 M solution of n-butyllithium in hexane were added slowly. The reaction solution was then warmed to −10° C. and stirred at this temperature for 10 min. The reaction solution was then once more cooled to −78° C., and 500 mg (2.32 mmol) of tert-butyl(4-methylphenyl)acetate, dissolved in 6 ml of THF, were added slowly. The reaction solution was then slowly warmed to −30° C. and then once more cooled to −78° C. Once this temperature had been reached, 596 mg (2.91 mmol) of 5-bromo-1,1,1-trifluoro-3-methylpentane were slowly added dropwise. After the addition had ended, the solution was slowly warmed to room temperature and stirred overnight. After TLC check (mobile phase cyclohexane/ethyl acetate 10:1), saturated ammonium chloride solution was added and the mixture was taken up in ethyl acetate. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate. After filtration, the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave 490 mg (1.48 mmol, 61% of theory) of a yellowish oil. The reaction solution was then warmed to −10° C. The reaction solution was then once more cooled to −78° C. were added slowly The reaction solution was then slowly warmed to −30° C. once more cooled to −78° C After the addition the solution was slowly warmed to room temperature stirred overnight The aqueous phase was extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate After filtration the solvent was removed under reduced pressure The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)