Methyl iodide → HCID 66973304, compound

Temperature

-78 °C

To a 1 M solution of sodium bis(trimethylsilyl)amide in THF (0.642 mL, 0.642 mmol) at −78° C. was added dropwise a solution of tert-butyl (2S)-2-(3,5-difluorophenyl)-6-oxopiperidine-1-carboxylate (200 mg, 0.642 mmol, described in Intermediate 26) in DME (10 mL) at −78° C. The resulting mixture was stirred at −78° C. for 10 min then iodomethane (0.040 mL, 0.642 mmol) was added. After stirring at −78° C. for 30 min and at −30° C. for 30 min, the reaction mixture was cooled to −78° C. and quenched with saturated aqueous NH4Cl (10 mL) and extracted with EtOAc (2×10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc-100:0 to 90:10. MS: m/z=270 (M−C4H7).

1. stirringAfter stirring at −78° C. for 30 min and at −30° C. for 30 min
2. temperaturethe reaction mixture was cooled to −78° C.
3. customquenched with saturated aqueous NH4Cl (10 mL)
4. extractionextracted with EtOAc (2×10 mL)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by silica gel chromatography
9. washeluting with a gradient of hexane

ORD record

ord-65918b507de949cc83300a388d24fde2

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07625901B2