2,6-Dibromopyridine → 1-(6-Bromo-2-pyridinyl)-2-(ethyloxy)ethanol

Temperature

-78 °C

To a solution of n-butyllithium (1.6M in hexanes, 4.19 mL, 6.70 mmol) in anhydrous THF (4.0 mL) under nitrogen at −78° C. was added a solution of 2,6-dibromopyridine (1.59 g, 6.71 mmol) in anhydrous THF (9.5 mL) drop-wise over 1 h. The resulting dark green solution was stirred at −78° C. for 15 min and then treated with N-ethyl-2-(ethyloxy)-N-(phenylmethyl)acetamide (1.93 g, 8.70 mmol), washing in with anhydrous THF (1.0 mL). The resulting green solution was stirred at −78° C. for 15 min and was then treated with a solution of AcOH (0.42 mL) in MeOH (7.00 mL) to give a orange solution which was then treated with NaBH4 (0.38 g, 10.04 mmol). This mixture was removed from the cooling bath and allowed to warm to room temperature over 2 h. The mixture was then treated with saturated aqueous. NH4Cl (50 mL) and the products extracted with EtOAc (2×50 mL). The combined organic layer was then washed with brine (100 mL), dried (MgSO4) and the reduced in vacuo to give a yellow oil. Purification by SPE (silica, 20 g cartridge) eluting with cyclohexane:EtOAc (gradient 50:1 to 1:1) afforded the title compound as a white solid (612 mg).

1. washwashing in with anhydrous THF (1.0 mL)
2. stirringThe resulting green solution was stirred at −78° C. for 15 min
3. additionwas then treated with a solution of AcOH (0.42 mL) in MeOH (7.00 mL)
4. customto give a orange solution which
5. customThis mixture was removed from the cooling bath
6. temperatureto warm to room temperature over 2 h
7. additionThe mixture was then treated with saturated aqueous
8. extractionNH4Cl (50 mL) and the products extracted with EtOAc (2×50 mL)
9. washThe combined organic layer was then washed with brine (100 mL)
10. dry with materialdried (MgSO4)
11. customto give a yellow oil
12. customPurification by SPE (silica, 20 g cartridge)
13. washeluting with cyclohexane

ORD record

ord-ba68a757769f49a7a61ef012a9d55f37

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07338960B2