2-acetylcyclohexan-1-one

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:0.00; pressure:0.00; stir:

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:0.00; pressure:0.00; stir:

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-acetylcyclohexanone (25 g, 0.18 mol), potassium carbonate (29.5 g, 0.21 mol) and benzyltriethylammonium chloride (0.8 g, 0.0035 mol) in toluene (70 ml) was added ethyl acrylate (29 ml, 27 g, 0.27 mol) at room temperature. The mixture was heated at 40° C. for 20 hours, filtered and partitioned between distilled water (200 ml) and toluene (200 ml). The organic layer was dried over magnesium sulphate, filtered and concentrated under reduced pressure to give the title compound as a brown oil, (41.7 g, 97%) . filtered partitioned between distilled water (200 ml) and toluene (200 ml) The organic layer was dried over magnesium sulphate filtered concentrated under reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-acetylcyclohexanone (9.6 g, 0.068 mol), potassium carbonate (11.3 g, 0.082 mol) and benzyltriethylammonium chloride (0.3 g, 0.0013 mol) in toluene (26 ml), was added benzyl acrylate (16.72 g, 0.103 mol) at room temperature. The mixture was heated at 40° C. for 20 hours, cooled, partitioned between water (200 ml) and toluene (200 ml) and toluene (200 ml) and the layers separated. The aqueous layer was extracted with toluene (2×200 ml), the combined organic extracts dried over magnesium sulphate, filtered and concentrated under reduced pressure to provide the title compound as a pale yellow oil, (20.7 g), Rf. 0.2 (silica, hexane/diethyl ether, 2:1). The crude product was used without further purification. cooled partitioned between water (200 ml) and toluene (200 ml) and toluene (200 ml) the layers separated The aqueous layer was extracted with toluene (2×200 ml) the combined organic extracts dried over magnesium sulphate filtered concentrated under reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-acetylcyclohexanone (100 g, 0.71 mol), potassium carbonate (118.3 g, 0.85 mol) and benzyltriethylammonium chloride (3.18 g, 0.014 mol) in toluene (280 ml), was added, in one portion, tert-butyl acrylate (137.1 g, 155.2 ml, 1.07 mol) at room temperature. The suspension was stirred at 40° C. for 18 hours, diluted with distilled water (1 L) and toluene (500 ml), and the layers separated. The aqueous layer was extracted with toluene (3×500 ml), the combined toluene extracts dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a brown oil, (197.8 g) Rf. 0.41 (silica, hexane/ethyl acetate, 3:1). The crude product was used without further purification. the layers separated The aqueous layer was extracted with toluene (3×500 ml) the combined toluene extracts dried over magnesium sulphate filtered concentrated under reduced pressure to give a brown oil, (197.8 g) Rf The crude product was used without further purification

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-(5-trifluoromethyl-pyridin-2-yl)-ethylamine (200 mg, 1.05 mmol) was added 6-bromo-1-methyl-1H-indole (685 mg, 2.10 mmol), cuprous iodide (10 mg, 0.05 mmol) and cesium carbonate (685 mg, 2.1 mmol) under an argon atmosphere. Then DMF (400 μl) and 2-acetylcyclohexanone (28 μl, 0.21 mmol) were added and the reaction mixture was stirred for 4 h at 120° C. After cooling to ambient temperature the reaction mixture was separated between tert-butylmethylether (2×20 ml) and water (15 ml). The combined organic layers were washed with brine (15 ml) and dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 67:33) afforded the title compound (114 mg, 34%) as a light brown oil. MS m/e: 320.1 [M+H]+. After cooling to ambient temperature the reaction mixture was separated between tert-butylmethylether (2×20 ml) and water (15 ml) The combined organic layers were washed with brine (15 ml) dried over sodium sulfate Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 67:33)