Carbon Dioxide → HCID 86628360, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 3-[4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-piperidinyl]-2-[6-fluoro-3-(methyloxy)-5-quinoxalinyl]propanoate (21.8 g, 47.2 mmol) in dry tetrahydrofuran (500 ml) was cooled in a CO2(s)/acetonitrile/water bath (−40 to −45° C.) and treated slowly with lithium aluminium hydride (1M in tetrahydrofuran, 76.2 ml). The mixture was stirred at −30 to −40° C. (internal temp.) for 7 h, with a further addition of lithium aluminium hydride (8 ml) after 5.5 h. Sodium hydroxide (2M) was added cautiously dropwise until a filterable precipitate was obtained. The mixture was diluted with ethyl acetate and filtered through kieselguhr, washed through with ethyl acetate and evaporated. The crude product was chromatographed on silica (1000 g), eluting with 0-6% methanol/dichloromethane to give the desired product (12.31 g), still containing some impurities, and later fractions containing a 1:1 mixture (7.58 g) of desired product and 1,1-dimethylethyl (1-{2-[6-fluoro-3-(methyloxy)-1,2-dihydro-5-quinoxalinyl]-3-hydroxypropyl}-4-piperidinyl)carbamate.

Provenance & Evidence