2,6-dimethylheptan-3-one

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

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of KOtBu (15.6 g, 139 mmol) in THF (200 mL) is added ethylformate (27.4 g, 370 mmol). During the addition, the mixture is cooled with a water bath to 10° C. Strong gas evolution occurs. The mixture is stirred until the gas evolution ceases (5 min) and is then cooled to −5° C. To this mixture a solution of 2,6-dimethyl-heptan-3-one (20 g, 141 mmol) and ethylformate (13.7 g, 185 mmol) in THF (20 mL) is added slowly during 30 min. The reaction mixture is stirred for 2 h and allowed to slowly warm to rt. The reaction is diluted with diethyl ether (200 mL) and washed with 1 N aq. HCl (2×100 mL). The organic extract is dried (Na2SO4), filtered and evaporated to give 1-hydroxy-2-isobutyl-4-methyl-pent-1-en-3-one (7.35 g) as a brown resin; LC-MS: tR=0.91 min, [M+1]=171.21. During the addition is then cooled to −5° C The reaction mixture is stirred for 2 h to slowly warm to rt washed with 1 N aq. HCl (2×100 mL) The organic extract is dried (Na2SO4) filtered evaporated

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

Procedure: To a slurry of Mg turnings (3.89 g, 160 mmol) in dry diethyl ether (150 mL), a solution of isoamylbromide (24.59 g, 163 mmol) in diethyl ether (20 mL) is slowly added. As soon as the reaction starts, the mixture is cooled if necessary with a water bath. After complete addition, the mixture is stirred for 30 min, and is then added slowly to a cooled (0° C.) mixture of isobutyronitrile (34.65 g, 501 mmol) and CuBr (1.15 g, 8.0 mmol) in diethyl ether (50 mL) and THF (50 mL). After complete addition (30 min) the mixture is stirred at rt for 1 h before 1 N aq. NaH2PO4 (50 mL) and 1N aq. HCl (100 mL) is added. Stirring is continued at rt for 15 min. The phases are separated and the aq. phase is extracted with additional diethyl ether (100 mL). The combined organic extracts are washed with aq. 1N aq. HCl (2×50 mL), sat. aq. NH4Cl/sat. aq. NaHCO3 1:1 (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered and evaporated to give crude 2,6-dimethyl-heptan-3-one (20.1 g) as an oil. the mixture is cooled if necessary with a water bath After complete addition is then added slowly to a cooled After complete addition (30 min) the mixture is added Stirring is continued at rt for 15 min The phases are separated the aq. phase is extracted with additional diethyl ether (100 mL) The combined organic extracts are washed with aq. 1N aq. HCl (2×50 mL), sat. aq. NH4Cl/ aq. NaHCO3 1:1 (2×50 mL) and brine (50 mL), dried over Na2SO4 filtered evaporated