1-Hydroxybenzotriazole → 2-(2-Morpholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic acid monoethyl ester

Participants

Reaction Steps

To a stirring suspension of N-Cyclohexylcarbodiimide, N′-methyl polystyrene resin (1.7 mmole/gram, 0.2353 g, 0.4 mmol) in 10 ml of methylene chloride was added the acid 1 (63.9 mg, 0.2 mmol) and HOBT (45.9 mg, 0.34 mmol) which was allowed to stir for 15 minutes at room temperature. Compound 2 (53.75 mg, 0.2 mmol) and DIEA (0.068 ml, 0.4 mmol) were added and the reaction was allowed to stir for 5 hours at room temperature. Then silicycle triamine™ (0.28 g, 1.0 mmol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered and the solvent was removed under reduced pressure. The crude product 3 was used without further purification. Crude compound 3 was dissolved in methylene chloride and Dess-Martin reagent (15% in methylene chloride, 1.13 g, 0.6 mmol) was added and the reaction was allowed to stir at room temperature for 3 hours. The excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was extracted with ethyl acetate and washed with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The product was purified using HPLC to yield 11.6 mg of final compound 4; LCMS retention time 2:77 minutes, M+1 (532.4).

Provenance & Evidence