(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

Temperatur

-78 °C

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).

1. additionwas added dropwise
2. stirringThe mixture was stirred another 2 h at −78° C
3. temperatureThe mixture was warmed up to rt slowly
4. customquenched by sat. NH4Cl solution (30 mL)
5. extractionextracted by diethyl ether (2×150 mL)
6. washThe combined organic layers were washed by brine (30 mL)
7. dry with materialdried over Na2SO4
8. filtrationAfter filtration and concentration
9. customthe residue was purified by ISCO (40 g column, 0˜25% EtOAc in Hexanes)

ORD-Eintrag

ord-aad48de85c9b43afa4e0ddf68c77e349

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08487108B2