反应详情

To a solution of acetonitrile (300 μL, 5.7 mmol) in THF (20 mL) at RT was added a solution of potassium 2-methylbutan-2-olate in toluene (1.7 M, 10.1 mL, 17.2 mmol) followed by the dropwise addition of methyl 4-methyltetrahydro-2H-pyran-4-carboxylate (1.36 g, 8.62 mmol) and the reaction mixture maintained at RT for 16 hr. The resulting mixture was concentrated in vacuo to a volume of ˜10 mL and was then diluted with EtOH (20 mL) and p-tolylhydrazine hydrochloride (911 mg, 5.74 mmol) was added. The reaction was acidified to pH 1 by the addition of conc hydrochloric acid and the resulting heterogeneous mixture was heated to 70° C. for 5 hr, was then cooled to RT and concentrated in vacuo to a volume of ˜20 mL. The mixture was diluted with water (30 mL) and adjusted to pH 12 by the addition of 2M aq NaOH and was then extracted with ethyl acetate (2×20 mL). The combined extracts were washed with brine (30 mL) and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, EtOAc in isohexane, 0-50%, gradient elution) to afford the title compound, Intermediate 21, as a yellow solid (550 mg, 32%); Rt 1.48 min (Method 2); m/z 272 (M+H)+, (ES+).

1. concentrationThe resulting mixture was concentrated in vacuo to a volume of ˜10 mL
2. additionwas added
3. temperaturethe resulting heterogeneous mixture was heated to 70° C. for 5 hr
4. temperaturewas then cooled to RT
5. concentrationconcentrated in vacuo to a volume of ˜20 mL
6. additionThe mixture was diluted with water (30 mL)
7. additionadjusted to pH 12 by the addition of 2M aq NaOH
8. extractionwas then extracted with ethyl acetate (2×20 mL)
9. washThe combined extracts were washed with brine (30 mL)
10. customdried
11. customevaporated in vacuo
12. customThe residue was purified by flash column chromatography (SiO2, EtOAc in isohexane, 0-50%, gradient elution)