Morpholine → 4-(5-Bromopyridin-3-yl)morpholine

Temperatur

120 °C

In a sealable tube, to a mixture of 3,5-dibromo-pyridine (3.3 g, 13.8 mmol) and NaOtBu (0.051 g, 23 mmol) in toluene (70 mL), is added morpholine (1.0 g, 11.5 mmol). The mixture is bubbled with Argon for 5 min, and then BINAP (428.9 mg, 0.69 mmol) and Pd2(dba)3 (210.2 mg, 0.23 mmol) are added. The reaction mixture is bubbled with Argon for another 5 min. Then the cap is sealed and the reaction mixture is heated at 120° C. overnight and then is cooled to room temperature. The reaction mixture is filtered through diatomaceous earth and washed with DCM. The filtrate is partitioned between water and DCM. The aqueous phase is further extracted with DCM (2×). The combined DCM phases are concentrated. The crude is purified by flash chromatography on a silica gel column (EtOAc/heptane 0 to 50% gradient, then 50%) to provide 1.42 g of 4-(5-bromo-3-pyridyl)morpholine.

1. customThe mixture is bubbled with Argon for 5 min
2. customThe reaction mixture is bubbled with Argon for another 5 min
3. customThen the cap is sealed
4. temperatureis cooled to room temperature
5. filtrationThe reaction mixture is filtered through diatomaceous earth
6. washwashed with DCM
7. customThe filtrate is partitioned between water and DCM
8. extractionThe aqueous phase is further extracted with DCM (2×)
9. concentrationThe combined DCM phases are concentrated
10. customThe crude is purified by flash chromatography on a silica gel column (EtOAc/heptane 0 to 50% gradient

ORD-Eintrag

ord-7a234e61718c4a5fb21caffcce39713f

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09181272B2