(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine → (2S,5R)-2-(((1r*,3R*,4R*)-3-(tert-butyldimethylsilyloxy)-4-fluorocyclopentyl)methyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

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Reaction Conditions

Reaction Steps

A solution of (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1.2 g, 1.5 equiv.) in dry THF (30 mL) was cooled to −78° C. n-BuLi (1.6 M in Hexane, 4.08 mL, 1.5 equiv.) was added dropwise. After stirring 1 h at −78° C., a solution of (±)-tert-butyl((1r,2R,4R)-2-fluoro-4-(iodomethyl)cyclopentyloxy)dimethylsilane (1.56 g, 4.36 mmol) in dry THF (8 mL) was added dropwise. The mixture was stirred another 2 h at −78° C. The mixture was warmed up to rt slowly, quenched by sat. NH4Cl solution (30 mL), extracted by diethyl ether (2×150 mL). The combined organic layers were washed by brine (30 mL), dried over Na2SO4. After filtration and concentration, the residue was purified by ISCO (40 g column, 0˜25% EtOAc in Hexanes) to afford (2S,5R)-2-(((1r*,3R*,4R*)-3-(tert-butyldimethylsilyloxy)-4-fluorocyclopentyl)methyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1.81 g, quant. yield) as a clear oil. MS ESI +ve m/z 415 (M+1).

Provenance & Evidence