Tetrahydrofuran → 4-(2-Methoxyethoxy)pyridin-2-amine

Temperature

60 °C

A steady stream of nitrogen was passed through a mixture of 2-chloro-4-(2-methoxyethoxy)pyridine (50.17 g, 267.4 mmol), Pd2dba3 (4.897 g, 5.348 mmol), XPHOS (5.099 g, 10.70 mmol) and tetrahydrofuran (445.7 ml) for 10 minutes. To the resulting degassed mixture was added lithium bis(trimethylsilyl)amide (561.5 ml, 561.5 mmol). After addition, the resulting mixture was heated to 60° C. for 18 hours. The reaction was cooled to ambient temperature and diluted with 1 N hydrochloric acid (200 mL). The resulting solution was washed twice with 500 ml of methyl-tert-butyl ether. The pH of the aqueous layer was taken to 11 with 6 N NaOH and was extracted with dichloromethane (3×500 ml). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to yield title compound. (35 g, 78% yield) MS APCI (+) m/z 169 (M+1) detected.

1. customTo the resulting degassed mixture
2. additionAfter addition
3. temperatureThe reaction was cooled to ambient temperature
4. washThe resulting solution was washed twice with 500 ml of methyl-tert-butyl ether
5. extractionwas extracted with dichloromethane (3×500 ml)
6. dry with materialThe combined organic layers were dried over MgSO4
7. concentrationconcentrated under reduced pressure

ORD record

ord-6719ec03783f471f80268227c79d7c52

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138181B2