Morpholine → 5-Morpholinopyridin-3-amine

Temperature

65 °C

To a stirred solution of 5-bromopyridin-3-amine (1.5 g, 8.67 mmol), X-Phos (0.33 g, 0.69 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.32 g, 0.35 mmol) and morpholine (3.78 g, 43.3 mmol) in THF (17.3 mL) was added a 1.0M solution of lithium bis(trimethylsilyl)amide in THF (47.7 mL, 47.7 mmol). The resulting mixture was heated to 65° C. and stirring continued for 3 h. After which, the reaction was cooled to rt and then poured into water (100 mL) and extracted with EtOAc (2×150 mL) and DCM (2×150 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (0 to 100% DCM in EtOAc) to give 5-morpholinopyridin-3-amine. Mass Spectrum (ESI) m/e=180.1 (M+1).

1. temperatureAfter which, the reaction was cooled to rt
2. extractionextracted with EtOAc (2×150 mL) and DCM (2×150 mL)
3. dry with materialThe combined organic layers were dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM in EtOAc)

ORD record

ord-6999f84ab3ab44a2892c858e2cf45bf7

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940724B2