Potassium Phosphate, Tribasic → Tert-butyl (5-cyclopropylpyridin-3-yl)methylcarbamate

Temperatur

100 °C

To a solution of tert-butyl (5-bromopyridin-3-yl)methylcarbamate (496 mg, 2 mmol), cyclopropyl boronic acid (223 mg, 2.6 mmol), potassium phosphate (1.49 g, 7.0 mmol) and tricyclohexyl phosphine (56 mg, 0.2 mmol) in toluene (9 mL) and water (0.45 mL) under a nitrogen atmosphere was added palladium acetate (22 mg, 0.1 mmol). The mixture was heated at 100° C. for 3 h and then cooled to rt. Water (20 mL) was added and the mixture extracted with EtOAc (2×30 mL), the combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. Crude product was purified by column chromatography (50% EtOAc in hexanes) afforded tert-butyl (5-cyclopropylpyridin-3-yl)methylcarbamate in 60% yield. (5-cyclopropylpyridin-3-yl)methanamine was then generated by removal of the Boc protecting group by treatment with HCl (in methanol or dioxane) or trifluoroacetic acid in dichloromethane.

1. temperaturecooled to rt
2. extractionthe mixture extracted with EtOAc (2×30 mL)
3. washthe combined organic extracts were washed with brine (20 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customCrude product was purified by column chromatography (50% EtOAc in hexanes)

ORD-Eintrag

ord-630338b639804e95a5a63921ec67b9b8

Quelldatensatz

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08299267B2