Potassium Carbonate → 2-[2-Fluoro-4-(4-pyrrolidin-1-yl-cyclohexyl)-phenyl]-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

温度

80 °C

2-[2-Fluoro-4-(4-methanesulfonyloxy-cyclohexyl)-phenyl]-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (Intermediate 28) (150 mg, 0.3 mmol, 1 equiv.) and pyrrolidine (84.3 mg, 1.19 mmol) were dissolved in anhydrous CH3CN (2 mL). To this colorless solution was added powder K2CO3 at r.t. The suspension was heated in an oil bath maintained at 80° C. for 24 h. The suspension was concentrated to dryness. The residue was taken in water (2 mL) and DCM (2 mL). The two layers were separated, and the aqueous layer was extracted with DCM (2 mL×2). The combined DCM extracts were washed with sodium bicarbonate (2 mL), brine (2 mL), dried (anhydrous potassium carbonate), filtered, and concentrated in vacuo. The crude product was purified on a silica gel column, eluted with 5% of MeOH in DCM and 5% 7N NH3 of MeOH solution in DCM to afford the title compound.

1. temperatureThe suspension was heated in an oil bath
2. concentrationThe suspension was concentrated to dryness
3. customThe two layers were separated
4. extractionthe aqueous layer was extracted with DCM (2 mL×2)
5. washThe combined DCM extracts were washed with sodium bicarbonate (2 mL), brine (2 mL)
6. dry with materialdried (anhydrous potassium carbonate)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified on a silica gel column
10. washeluted with 5% of MeOH in DCM and 5% 7N NH3 of MeOH solution in DCM

ORDレコード

ord-99b103c4ed4144eb85ebbd384556f526

出典データセット

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08735385B2