2,6-Dimethyl-4-pyranone → cis-2,6-dimethyloxan-4-one

Beteiligte Stoffe

Reaktionsschritte

A solution of 2,6-dimethyl-4-pyrone (5.0 g, 40.3 mmol) in ethanol was charged with Pd/C (0.86 g, 0.40 mmol). The mixture was subjected to pressurized H2 conditions using a parr hydrogenator (50 psi) and the mixture was shaken overnight. Afterwards, the mixture was filtered through a pad of celite, and the filtrate was concentrated. The crude material was purified by column chromatography using 5% to 60% EtOAc-hexanes eluent. The desired fractions were combined and concentrated to give cis-2,6-dimethyldihydro-2H-pyran-4(3H)-one as a colorless oil. Step 2: A solution of cis-2,6-dimethyldihydro-2H-pyran-4(3H)-one (2.05 g, 16.0 mmol) and hydroxylamine chloride (0.73 mL, 17.6 mmol) in methanol was heated to 60° C. for 2 h. After the mixture was cooled to RT, a spatula full of Raney nickel (0.19 g, 3.20 mmol) was added to the reaction mixture. The reaction was subjected to H2 atmosphere using a balloon. The mixture was stirred overnight at 50° C. The reaction mixture was filtered through a pad of celite. The filtrate was acidified with HCl (4.0 mL, 15.99 mmol)-4N in dioxane, and the resulting solution was concentrated. The resulting solid was washed with ether and filtered to give cis-2,6-dimethyltetrahydro-2H-pyran-4-amine hydrochloride as a white solid. The titled compound was prepared by following the procedure described in Example 10, Step 2 to give (2R)-3-(2-amino-6-o-tolylquinolin-3-yl)-N-(cis-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-methylpropanamide. MS (ESI, pos. ion) m/z: 433 (M+1).

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