Diisopropylethylamine → {(S)-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-3-methyl-butyl}-carbamic acid t-butyl ester

関与物質

反応手順

A solution of N-t-butoxycarbonyl-(L)-leucine mono-hydrate (2.81 g, 11.28 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 2.02 g, 13 mmol) in N,N-dimethylformamide (15 mL) was treated with N,N-diisopropylethylamine (3.5 mL, 20 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (8.84 g, 20 mmol) and stirred at room temperature for 12 h. At this time the mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and a concentrated ammonium chloride solution. The layers were separated and the organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue purified by ISCO flash chromatography (RediSep silica 120 g, 20% to 80% ethyl acetate/hexanes) which afforded {(S)-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-3-methyl-butyl}-carbamic acid t-butyl ester (4.15 g, 100%) as a white solid.

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