4-hydroxy-3,3-dimethylbutan-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 23.7 g 4-Hydroxy-3,3-dimethyl-butan-2-one was dissolved in 150 ml. DCM. 49.5 mL (3 eq) pyridine and 17.5 mL (1.1 eq) mesylchloride were added and the mixture was stirred at room temperature for 20 hours. The suspension was filtered and the filter cake was washed two times with DCM. The filtrate was washed with 1 M HCl and the aqueous layer was extracted two times with DCM. The combined filtrates were dried over Na2SO4 and the solvent was evaporated under reduced pressure to give 41.2 g of a brown liquid. 1H NMR (400 MHz, CDCl3) δ 1.24 (s, 6H), 2.20 (s, 3H), 3.03 (s, 3H), 4.21 (s, 2H). The suspension was filtered the filter cake was washed two times with DCM The filtrate was washed with 1 M HCl the aqueous layer was extracted two times with DCM The combined filtrates were dried over Na2SO4 the solvent was evaporated under reduced pressure

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

実験手順: 232 g (2 mol) of 3,3-dimethyl-4-hydroxy-2-butanone (for the preparation, see Beilstein H 1 E III 3239, IV 4030 and Bull.Soc. Chim. France 1964, 2849) were reacted with 229 g (2 mol) of methanesulphonyl chloride in 700 ml of absolute pyridine at 0° to 5° C. After leaving the mixture to stand at 20° C. for 12 hours, it was diluted with methylene chloride and extracted by shaking with ice-water. The organic phase was dried, and freed from solvent in vacuo, and the residue was fractionated over a column. 332 g (86% of theory) of 2,2-dimethyl-3-oxo-butyl methanesulphonate of boiling point 106°-120° C./0.12 mm Hg were obtained. After leaving the mixture extracted The organic phase was dried

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

実験手順: 232 g (2 mol) of 3,3-dimethyl-4-hydroxy-butan-2-one (for the preparation, see Beilstein H 1 E III 3239, IV 4030 and Bull. Soc. Chim. France 1964, 2849) were reacted with 229 g (2 mol) of methanesulphonyl chloride in 700 ml of absolute pyridine at 0° to 5° C. After leaving the mixture to stand at 20° C. for 12 hours, it was diluted with methylene chloride and extracted by shaking with ice-water. The organic phase was dried and freed from solvent in vacuo and the residue was fractionated over a column. 332 g (86% of theory) of 2,2-dimethyl-3-oxo-butyl methanesulphonate of boiling point 106°-120° C./0.12 mm Hg were obtained. ##STR22## After leaving the mixture extracted The organic phase was dried

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

実験手順: Bromine (182.0 g, 1.1 mol) is slowly added at −10° C. to a solution of 4-hydroxy-3,3-dimethyl-butan-2-one (120.0 g, 1.0 mol) in 700.0 mL of MeOH. The solution is slowly warmed up to room temperature and the reaction mixture is stirred for 2 h. Ethyl acetate and water are added to the reaction mixture, the two phases are separated, and the organic layer is washed with 10% K2CO3 solution. The organic layer is dried over anhydrous Na2SO4 and after filtration the solvent is removed under reduced pressure to afford the crude product that is purified by silica gel chromatography to afford 100.0 g of 1-bromo-4-hydroxy-3,3-dimethyl-butan-2-one as a brown liquid. Yield: 44%, over two steps; m/z 197 [M+H]. the two phases are separated the organic layer is washed with 10% K2CO3 solution The organic layer is dried over anhydrous Na2SO4 after filtration the solvent is removed under reduced pressure to afford the crude product that is purified by silica gel chromatography

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

実験手順: To a solution of 4-hydroxy-3,3-dimethylbutan-2-one (9.7 g, 84 mmol) and DIPEA (16.04 mL, 92 mmol) in DCM (50 mL) cooled to 0° C. was dropwise added methanesulfonyl chloride (7.16 mL, 92 mmol). The reaction mixture was stirred at rt for 18 h. The reaction mixture was diluted with EtOAc and washed with sat. NaHCO3, sat. NaCl, dried (MgSO4), filtered and concentrated to yield 2,2-dimethyl-3-oxobutyl methanesulfonate (14.6 g). 1H NMR (400 MHz, CDCl3) δ ppm 4.21 (2H, s), 3.04 (3H, s), 2.21 (3H, s), 1.25 (6H, s). washed with sat. NaHCO3, sat. NaCl dried (MgSO4) filtered concentrated

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

実験手順: To a solution of 4-hydroxy-3,3-dimethylbutan-2-one (9.7 g, 84 mmol) and DIPEA (16.04 mL, 92 mmol) in DCM (50 mL) cooled to 0° C. was dropwise added methanesulfonyl chloride (7.16 mL, 92 mmol). The reaction mixture was stirred at rt for 18 h. The reaction mixture was diluted with EtOAc and washed with sat. NaHCO3, sat. NaCl, dried (MgSO4), filtered and concentrated to yield 2,2-dimethyl-3-oxobutyl methanesulfonate (14.6 g). 1H NMR (400 MHz, CDCl3) δ ppm 4.21 (2H, s), 3.04 (3H, s), 2.21 (3H, s), 1.25 (6H, s). washed with sat. NaHCO3, sat. NaCl dried (MgSO4) filtered concentrated

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

実験手順: 47.6 g (0.25 mol) of 4-toluenesulphonyl chloride were dissolved in 100 ml of chloroform, 35 g (0.3 mol) of 2,2-dimethyl-1-hydroxy-butan-3-one were added, and 40 ml (0.5 mol) of pyridine were added dropwise at 0° to 50° C. The reaction mixture was subsequently stirred at room temperature for 15 hours and poured on to 200 g of ice and 70 ml of concentrated hydrochloric acid and the organic phase was separated off, rinsed three times with 200 ml of water each time, dried over sodium sulphate and concentrated. The residue was taken up in 100 ml of petroleum ether, whereupon the end product crystallized out. 46 g (71% of theory) of 2,2-dimethyl-1-tosyloxy-butan-3-one were obtained as colorless crystals of melting point 49° to 52° C. ##STR815## the organic phase was separated off rinsed three times with 200 ml of water each time dried over sodium sulphate concentrated crystallized out

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

実験手順: 47.6 g (0.25 mol) of 4-toluenesulphonyl chloride were dissolved in 100 ml of chloroform, 35 g (0.3 mol) of 2,2-dimethyl-1-hydroxy-butan-3-one were added, and 40 ml (0.5 mol) of pyridine were added dropwise at 0° to 50° C. The reaction mixture was subsequently stirred at room temperature for 15 hours and poured on to 200 g of ice and 70 ml of concentrated hydrochloric acid and the organic phase was separated off, rinsed three times with 200 ml of water each time, dried over sodium sulphate and concentrated. The residue was taken up in 100 ml of petroleum ether, whereupon the end product crystallized out. 46 g (71% of theory) of 2,2-dimethyl-1-tosyloxy-butan-3-one were obtained as colorless crystals of melting point 49° to 52° C. ##STR815## the organic phase was separated off rinsed three times with 200 ml of water each time dried over sodium sulphate concentrated crystallized out

反応条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,3-Dimethyl-4-hydroxybutan-2-one (11.2 g) was dissolved in 50 ml of dimethyl sulfoxide, and nitrogen gas was passed therethrough for 20 minutes. Then, 18.2 g of 3-trifluoromethyl-6-chloropyridine and 15 g of anhydrous potassium carbonate were added thereto, and the solution was gradually heated to 115° C. and reacted under stirring for 4 hours at that temperature. After completion of the reaction, the product was put into ice water, extracted with methylene chloride, washed with water and dried over Glauber's salt. The solvent was distilled off to give 24.8 g of oily 3,3-dimethyl-4-(5-trifluoromethylpyridine-2-yloxy)butan-2-one. reacted After completion of the reaction extracted with methylene chloride washed with water dried over Glauber's salt The solvent was distilled off

反応条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,3-Dimethyl-4-hydroxybutan-2-one (11.2 g) was dissolved in 50 ml of dimethyl sulfoxide, and nitrogen gas was passed therethrough for 20 minutes. Then, 18.2 g of 3-trifluoromethyl-6-chloropyridine and 15 g of anhydrous potassium carbonate were added thereto, and the solution was gradually heated to 115° C. and reacted under stirring for 4 hours at that temperature. After completion of the reaction, the product was put into ice water, extracted with methylene chloride, washed with water and dried over Glauber's salt. The solvent was distilled off to give 24.8 g of oily 3,3-dimethyl-4-(5-trifluoromethylpyridine-2-yloxy)butan-2-one. reacted After completion of the reaction extracted with methylene chloride washed with water dried over Glauber's salt The solvent was distilled off