Ammonium Chloride → (8R, 9R)-8-(t-Butydimethylsilyloxy)-6-methoxymethyl-2,3-dimethyl-9-phenyl-5,6,7,8,9,10-hexahydroimidazo[1,2-h][1,7]naphthyridin-7-one

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Reaction Conditions

Reaction Steps

By using a water separator, a mixture of 2.66 g of 6-methoxymethyl-2,3-dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-one, 4.27 g of ethyl (2R, 3R)-3-amino-2-(t-butyldimethylsilyloxy)-3-phenylpropionate, 70 mg of p-toluenesulfonic acid and 15 ml of toluene is boiled at reflux for 1.5 h. After cooling, 15 ml of tetrahydrofuran are added. With introduction of argon, the mixture is cooled to an internal temperature of −25° C. 15.4 ml of a commercial 2 molar solution of lithium diisopropylamide (Aldrich) are then added. The solution is stirred at −25° C. for 30 min. The solution is then allowed to warm to room temperature (30 min.) and poured into 30 ml of saturated aqueous ammonium chloride solution, the mixture is extracted three times with in each case 20 ml of ethyl acetate and the combined extracts are concentrated to dryness in vacuo. Purification on silica gel (mobile phase: methylene chloride/methanol=100/3) gives 5.2 g of the title compound as a yellowish amorphous solid. 1H-NMR(CDCl3, δ), 7.33-7.45 (m, 5H), 5.95 (d, 1H), 4.55-4.65 (dd, 1H), 4.2-4.4 (dd, 2H), 3.2-3.75 (m, 3H), 3.3 (s, 3H), 2.91-3.1 (q, 1H), 2.15 (s, 6H), 0.6 (d, 9H), 0.08 (d, 3H), −0.3 (d, 3H).

Provenance & Evidence