5-(cyclopentanecarbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of cyclopentanecarbonyl chloride (1.100 mL, 9.05 mmol) in DCM (5 mL) was added dropwise to a stirred solution of isopropylidene malonate (1.304 g, 9.05 mmol), and pyridine (1.464 mL, 18.10 mmol) in DCM (20 mL) at 5° C., over a period of 10 minutes under nitrogen. The resulting solution was stirred at 5° C. for 1 hour and then allowed to warm to 20° C. and stirred for another hour. The reaction mixture was diluted with DCM (100 mL), and washed sequentially with 2M HCl (2×50 mL), water (50 mL), and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product, 5-(cyclopentanecarbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (2.100 g, 97%) as a brown oil. to warm to 20° C. stirred for another hour washed sequentially with 2M HCl (2×50 mL), water (50 mL), and saturated brine (50 mL) The organic layer was dried over MgSO4 filtered evaporated

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Adamantanamine hydrochloride (1.641 g, 8.74 mmol) was added to 5-(cyclopentanecarbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate #77), (2.1 g, 8.74 mmol) and N-Ethyldiisopropylamine (1.512 mL, 8.74 mmol) in toluene (30 mL). The resulting suspension was stirred at 110° C. for 2 hours. The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with 2M HCl (20 mL), and water (2×50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford N-(2-adamantyl)-3-cyclopentyl-3-oxo-propanamide (1.030 g, 40.7%) as a brown oil which crystallised on standing. washed sequentially with 2M HCl (20 mL), and water (2×50 mL) The organic layer was dried over MgSO4 filtered evaporated to afford crude product The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane Pure fractions were evaporated to dryness

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of cyclopentanecarbonyl chloride (1.100 mL, 9.05 mmol) in DCM (5 mL) was added dropwise to a stirred solution of isopropylidene malonate (1.304 g, 9.05 mmol), and pyridine (1.464 mL, 18.10 mmol) in DCM (20 mL) at 5° C., over a period of 10 minutes under nitrogen. The resulting solution was stiffed at 5° C. for 1 hour and then allowed to warm to 20° C. and stirred for another hour. The reaction mixture was diluted with DCM (100 mL), and washed sequentially with 2M HCl (2×50 mL), water (50 mL), and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product, 5-(cyclopentanecarbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (2.100 g, 97%) as a brown oil. washed sequentially with 2M HCl (2×50 mL), water (50 mL), and saturated brine (50 mL) The organic layer was dried over MgSO4 filtered evaporated

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Adamantanamine hydrochloride (1.641 g, 8.74 mmol) was added to 5-(cyclopentanecarbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate#77), (2.1 g, 8.74 mmol) and N-Ethyldiisopropylamine (1.512 mL, 8.74 mmol) in toluene (30 mL). The resulting suspension was stirred at 110° C. for 2 hours. The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with 2M HCl (20 mL), and water (2×50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford N-(2-adamantyl)-3-cyclopentyl-3-oxo-propanamide (1.030 g, 40.7%) as a brown oil which crystallised on standing. washed sequentially with 2M HCl (20 mL), and water (2×50 mL) The organic layer was dried over MgSO4 filtered evaporated to afford crude product The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane Pure fractions were evaporated to dryness