Sodium hydride → HCID 178459923, compound

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Reaction Steps

4-[(1E,3E)-4-[trans-5-[[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-1,3-butadienyl]-3-fluorobenzonitrile (570 mg, 1.05 mmol) obtained from Example Reference example 1 was dissolved in N,N-dimethylformamide (3 ml), and sodium hydride (ca. 30 mg, 1.3 mmol) was added thereto at room temperature. The mixture was stirred for 1 hour, then 4-(allyloxycarbonyloxy)butyryl chloride (250 mg, 1.21 mmol) obtained from Example 11-(2) was added thereto, and the mixture was stirred further for 1 hour. The mixture was diluted with ethyl acetate, and a saturated aqueous solution of ammonium chloride was poured thereinto. The organic layer was separated, washed with an aqueous solution of sodium hydrogen carbonate and then with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform] to afford the title compound (562 mg, 75% yield) as a colorless amorphous solid.

Provenance & Evidence