1-(4-bromophenyl)-2-methylpropan-2-ol

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(4-bromophenyl)-2-methyl-propan-2-ol (2.77 g, 12.1 mmol) was dissolved in dry THF (30 mL) and the solution was cooled to −78° C. Tert-butyllithium in pentane (15 mL of 1.7 M, 25.4 mmol) was added dropwise over 10 minutes and the reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was added via cannula to crushed solid CO2 (53.2 g, 1.21 mol) in Et2O under a flow of nitrogen gas. The reaction mixture was allowed to warm to room temperature, diluted with EtOAc and washed with water. The aqueous phase was acidified (pH 2) with 1N HCl solution and the aqueous layer was extracted with EtOAc. The organics were dried over sodium sulfate, filtered and concentrated in vacuo to give 4-(2-hydroxy-2-methyl-propyl)benzoic acid (620 mg, 26%) as a white solid. ESI-MS m/z calc. 194.0. found 195.3 (M+1)+; Retention time: 0.93 minutes (3 min run). The reaction mixture was added via cannula to warm to room temperature washed with water the aqueous layer was extracted with EtOAc The organics were dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromo(methyl)magnesium in diethyl ether (25 mL of 3 M, 74.5 mmol) in THF (8 mL) and toluene (25 mL) was added to a solution of ethyl 2-(4-bromophenyl)acetate (8.23 g, 33.9 mmol) in Et2O (165 mL) and the reaction mixture was stirred at 40° C. for 1 hour. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) and the phases were separated. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes to give 1-(4-bromophenyl)-2-methyl-propan-2-ol (5.68 g, 73%), as a clear oil. ESI-MS m/z calc. 228.1. found 229.5 (M+1)+; Retention time: 1.45 minutes (3 min run). The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) the phases were separated The organics were dried over sodium sulfate filtered concentrated in vacuo The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromo(methyl)magnesium in diethyl ether (25 mL of 3 M, 74.5 mmol) in THF (8 mL) and toluene (25 mL) was added to a solution of ethyl 2-(4-bromophenyl)acetate (8.23 g, 33.9 mmol) in Et2O (165 mL) and the reaction mixture was stirred at 40° C. for 1 hour. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) and the phases were separated. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes to give 1-(4-bromophenyl)-2-methyl-propan-2-ol (5.68 g, 73%), as a clear oil. ESI-MS m/z calc. 228.1. found 229.5 (M+1)+; Retention time: 1.45 minutes (3 min run). The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) the phases were separated The organics were dried over sodium sulfate filtered concentrated in vacuo The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes

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

実験手順: A solution of 4-bromophenylacteone (6.85 g, 32 mmol) in diethyl-ether (100 ml) was cooled to 0° C. and treated with methylmagnesium bromide (23.5 ml of a 3M solution in diethyl-ether, 70 mmol). The reaction mixture was allowed to warm gradually to room temperature. After 2 hours the reaction was quenched by addition of saturated aqueous ammonium chloride (200 ml). The organic phase was separated and washed with saturated sodium chloride (100 ml), dried (sodium sulfate) and reduced in vacuo. Purification by flash column chromatography on silica gel eluting with pentane:dichloromethane (60:40 changing to 0:100, by volume) gave the title compound as a colourless oil (6.23 g, 84%). After 2 hours the reaction was quenched by addition of saturated aqueous ammonium chloride (200 ml) The organic phase was separated washed with saturated sodium chloride (100 ml) dried (sodium sulfate) Purification by flash column chromatography on silica gel eluting with pentane:dichloromethane (60:40 changing to 0:100, by volume)

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

実験手順: A solution of 4-bromophenylacteone (6.85 g, 32 mmol) in diethyl-ether (100 ml) was cooled to 0° C. and treated with methylmagnesium bromide (23.5 ml of a 3M solution in diethyl-ether, 70 mmol). The reaction mixture was allowed to warm gradually to room temperature. After 2 hours the reaction was quenched by addition of saturated aqueous ammonium chloride (200 ml). The organic phase was separated and washed with saturated sodium chloride (100 ml), dried (sodium sulfate) and reduced in vacuo. Purification by flash column chromatography on silica gel eluting with pentane:dichloromethane (60:40 changing to 0:100, by volume) gave the title compound as a colourless oil (6.23 g, 84%). After 2 hours the reaction was quenched by addition of saturated aqueous ammonium chloride (200 ml) The organic phase was separated washed with saturated sodium chloride (100 ml) dried (sodium sulfate) Purification by flash column chromatography on silica gel eluting with pentane:dichloromethane (60:40 changing to 0:100, by volume)

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

実験手順: A solution of 4-bromophenylacteone (6.85 g, 32 mmol) in diethyl-ether (100 ml) was cooled to 0° C. and treated with methylmagnesium bromide (23.5 ml of a 3M solution in diethyl-ether, 70 mmol). The reaction mixture was allowed to warm gradually to room temperature. After 2 hours the reaction was quenched by addition of saturated aqueous ammonium chloride (200 ml). The organic phase was separated and washed with saturated sodium chloride (100 ml), dried (sodium sulfate) and reduced in vacuo. Purification by flash column chromatography on silica gel eluting with pentane:dichloromethane (60:40 changing to 0:100, by volume) gave the title compound as a colourless oil (6.23 g, 84%). After 2 hours the reaction was quenched by addition of saturated aqueous ammonium chloride (200 ml) The organic phase was separated washed with saturated sodium chloride (100 ml) dried (sodium sulfate) Purification by flash column chromatography on silica gel eluting with pentane:dichloromethane (60:40 changing to 0:100, by volume)

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

実験手順: A solution of 3.5 g (15.4 mmol) of 1-(4-bromophenyl)-2-methyl-propan-2-ol in 20 ml of glacial acetic acid was treated with 630 mg (15.4 mmol) of acetonitrile and cooled in ice. 10 ml of concentrated sulfuric acid was added slowly and the mixture stirred for 72 hours. The mixture was poured into 300 ml of ice/water and neutralised with potassium carbonate. The product was extracted with diethyl ether (2×250 ml). The combined organic phases were dried over magnesium sulfate, filtered and evaporated. The product was purified by recrystallisation from diethyl ether/hexane to give 3.3 g (80%) of N-[2-(4-bromophenyl)-1,1-dimethyl-ethyl]acetamide as a white solid. [Mass spectrum (ESI) MH+ =270]. cooled in ice The product was extracted with diethyl ether (2×250 ml) The combined organic phases were dried over magnesium sulfate filtered evaporated The product was purified by recrystallisation from diethyl ether/hexane

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4 g (16.5 mmol) of ethyl 4-bromophenylacetate in 60 ml of diethyl ether was treated with 26 ml (36.4 mmol) of a 1.4M solution of methylmagnesium bromide in toluene/tetrahydrofuran (3:1) and the mixture heated at 40° C. for 1 hour and then cooled. 100 ml of saturated aqueous ammonium chloride were added and the phases separated. The organic phase was dried over magnesium sulfate, filtered and evaporated to give 3.5 g (93%) of 1-(4-bromophenyl)-2-methyl-propan-2-ol as a colorless oil. [Mass spectrum (ESI) MH+ =229]. cooled the phases separated The organic phase was dried over magnesium sulfate filtered evaporated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(4-bromophenyl)-2-methyl-propan-2-ol (2.77 g, 12.1 mmol) was dissolved in dry THF (30 mL) and the solution was cooled to −78° C. Tert-butyllithium in pentane (15 mL of 1.7 M, 25.4 mmol) was added dropwise over 10 minutes and the reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was added via cannula to crushed solid CO2 (53.2 g, 1.21 mol) in Et2O under a flow of nitrogen gas. The reaction mixture was allowed to warm to room temperature, diluted with EtOAc and washed with water. The aqueous phase was acidified (pH 2) with 1N HCl solution and the aqueous layer was extracted with EtOAc. The organics were dried over sodium sulfate, filtered and concentrated in vacuo to give 4-(2-hydroxy-2-methyl-propyl)benzoic acid (620 mg, 26%) as a white solid. ESI-MS m/z calc. 194.0. Found 195.3 (M+1)+; Retention time: 0.93 minutes (3 min run). The reaction mixture was added via cannula to warm to room temperature washed with water the aqueous layer was extracted with EtOAc The organics were dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromo(methyl)magnesium in diethyl ether (25 mL of 3 M, 74.5 mmol) in THF (8 mL) and toluene (25 mL) was added to a solution of ethyl 2-(4-bromophenyl)acetate (8.23 g, 33.9 mmol) in Et2O (165 mL) and the reaction mixture was stirred at 40° C. for 1 hour. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) and the phases were separated. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes to give 1-(4-bromophenyl)-2-methyl-propan-2-ol (5.68 g, 73%), as a clear oil. ESI-MS m/z calc. 228.1. Found 229.5 (M+1)+; Retention time: 1.45 minutes (3 min run). The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) the phases were separated The organics were dried over sodium sulfate filtered concentrated in vacuo The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(4-bromophenyl)-2-methyl-propan-2-ol (2.77 g, 12.1 mmol) was dissolved in dry THF (30 mL) and the solution was cooled to −78° C. Tert-butyllithium in pentane (15 mL of 1.7 M, 25.4 mmol) was added dropwise over 10 minutes and the reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was added via cannula to crushed solid CO2 (53.2 g, 1.21 mol) in Et2O under a flow of nitrogen gas. The reaction mixture was allowed to warm to room temperature, diluted with EtOAc and washed with water. The aqueous phase was acidified (pH 2) with 1N HCl solution and the aqueous layer was extracted with EtOAc. The organics were dried over sodium sulfate, filtered and concentrated in vacuo to give 4-(2-hydroxy-2-methyl-propyl)benzoic acid (620 mg, 26%) as a white solid. ESI-MS m/z calc. 194.0. found 195.3 (M+1)+; Retention time: 0.93 minutes (3 min run). The reaction mixture was added via cannula to warm to room temperature washed with water the aqueous layer was extracted with EtOAc The organics were dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromo(methyl)magnesium in diethyl ether (25 mL of 3 M, 74.5 mmol) in THF (8 mL) and toluene (25 mL) was added to a solution of ethyl 2-(4-bromophenyl)acetate (8.23 g, 33.9 mmol) in Et2O (165 mL) and the reaction mixture was stirred at 40° C. for 1 hour. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) and the phases were separated. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes to give 1-(4-bromophenyl)-2-methyl-propan-2-ol (5.68 g, 73%), as a clear oil. ESI-MS m/z calc. 228.1. found 229.5 (M+1)+; Retention time: 1.45 minutes (3 min run). The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) the phases were separated The organics were dried over sodium sulfate filtered concentrated in vacuo The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes