1-cyclohexylpropan-2-one

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

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

Procedure: Cyclohexylacetone (300 mg, 2.14 mmol) in MeOH (5 mL) was treated with pyrrolidone hydrotribromide (1.3 g, 4.28 mmol) and the reaction was stirred at RT overnight. To the resulting solution of crude alpha-bromoketone in MeOH (without workup) was directly added solid sodium bicarbonate to neutralize the acid formed in the bromination step. To this neutralized bromoketone mixture was added 3-[1-(5-ethyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester (150 mg) in THF (2 mL) and the reaction was stirred for 1 h at RT. The solvent was removed at reduced pressure and the residue was dissolved in water and ethyl acetate. The aq portion was extracted two times with EtOAc, and the combined organic portion was washed with brine and then dried over sodium sulfate. Solvent removal under reduced pressure gave the crude product which was partially purified by silica gel chromatography (eluent: 10:1 hexanes:EtOAc) to give the aminothiazole derivative (300 mg). formed in the bromination step the reaction was stirred for 1 h at RT The solvent was removed at reduced pressure the residue was dissolved in water The aq portion was extracted two times with EtOAc the combined organic portion was washed with brine dried over sodium sulfate Solvent removal under reduced pressure gave the crude product which was partially purified by silica gel chromatography (eluent: 10:1 hexanes:EtOAc)

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

Procedure: Cyclohexylacetone (300 mg, 2.14 mmol) in MeOH (5 mL) was treated with pyrrolidone hydrotribromide (1.3 g, 4.28 mmol) and the reaction was stirred at RT overnight. To the resulting solution of crude alpha-bromoketone in MeOH (without workup) was directly added solid sodium bicarbonate to neutralize the acid formed in the bromination step. To this neutralized bromoketone mixture was added 3-[1-(5-ethyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester (150 mg) in THF (2 mL) and the reaction was stirred for 1 h at RT. The solvent was removed at reduced pressure and the residue was dissolved in water and ethyl acetate. The aq portion was extracted two times with EtOAc, and the combined organic portion was washed with brine and then dried over sodium sulfate. Solvent removal under reduced pressure gave the crude product which was partially purified by silica gel chromatography (eluent: 10:1 hexanes:EtOAc) to give the aminothiazole derivative (300 mg). formed in the bromination step the reaction was stirred for 1 h at RT The solvent was removed at reduced pressure the residue was dissolved in water The aq portion was extracted two times with EtOAc the combined organic portion was washed with brine dried over sodium sulfate Solvent removal under reduced pressure gave the crude product which was partially purified by silica gel chromatography (eluent: 10:1 hexanes:EtOAc)

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

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

Procedure: A 500 ml flask was charged with 120 g xylene, 33.8 g of solid potassium methylate (3.2 molar equivalent) and 34.0 g of dimethylcarbonate (2.5 molar equivalent). The slurry was heated to 50° C. and over the course of 4 hours 24.2 g of 1-cyclohexylpropan-2-one (87% GC, 1 molar equivalent) was added. Stirring was continued for 2 hours and then the reaction mixture was cooled to 25° C. 95 g of an acetic acid/water mixture (1:2) was then added carefully. After decantation the aqueous phase was drained and the organic phase concentrated. The crude product was distilled leading to 24.9 g of methyl 4-cyclohexyl-3-oxobutanoate (81% GC, 68% yield). was added the organic phase concentrated The crude product was distilled

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

Procedure: To a mixture of 43.5 parts of magnesium in 125 parts by volume of ether is added a portion of a solution containing 84 parts of methyl cyclohexylmethyl ketone and 71.4 parts of propargyl bromide in a solution consisting of 60 parts by volume of benzene and 180 parts by volume of ether. After the addition of 0.05 part of mercuric chloride to initiate the reaction, the remainder of the reactants is added dropwise. The reaction mixture is heated at the reflux temperature for about 15 minutes, allowed to cool to room temperature, then poured carefully into cold dilute hydrochloric acid. The aqueous phase is separated, extracted with ether and the combined ether extracts are washed successively with water, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and evaporated to dryness. Vacuum distillation of the residue affords 4(RS)-4-cyclohexylmethyl-4-methyl-1-butyn-4-ol. is added a portion of a solution the reaction the remainder of the reactants is added dropwise The reaction mixture is heated at the reflux temperature for about 15 minutes The aqueous phase is separated extracted with ether the combined ether extracts are washed successively with water, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride dried over anhydrous sodium sulfate evaporated to dryness Vacuum distillation of the residue

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

Procedure: Cyclohexylacetone (300 mg, 2.14 mmol) in MeOH (5 mL) was treated with pyrrolidone hydrotribromide (1.3 g, 4.28 mmol) and the reaction was stirred at RT overnight. To the resulting solution of crude alpha-bromoketone in MeOH (without workup) was directly added solid sodium bicarbonate to neutralize the acid formed in the bromination step. To this neutralized bromoketone mixture was added 3-[1-(5-ethyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester (150 mg) in THF (2 mL) and the reaction was stirred for 1 h at RT. The solvent was removed at reduced pressure and the residue was dissolved in water and ethyl acetate. The aq portion was extracted two times with EtOAc, and the combined organic portion was washed with brine and then dried over sodium sulfate. Solvent removal under reduced pressure gave the crude product which was partially purified by silica gel chromatography (eluent: 10:1 hexanes:EtOAc) to give the aminothiazole derivative (300 mg). formed in the bromination step the reaction was stirred for 1 h at RT The solvent was removed at reduced pressure the residue was dissolved in water The aq portion was extracted two times with EtOAc the combined organic portion was washed with brine dried over sodium sulfate Solvent removal under reduced pressure gave the crude product which was partially purified by silica gel chromatography (eluent: 10:1 hexanes:EtOAc)