2,6-Dibromopyridine → HCID 86059385, compound

Temperature

-78 °C

Under a nitrogen atmosphere, dissolve 2,6-dibromopyridine (10 g, 42.4 mmol) in anhydrous DCM (250 mL). Cool to −78° C. Add a solution of n-BuLi (1.6 M in hexanes) (29 mL, 46.2 mmol) very slowly via a syringe. After the addition, stir the reaction at −78° C. for 1 hr. Add a solution of 4-dimethylamino-cyclohexanone (5.4 g, 38.5 mmol) in anhydrous DCM (10 mL) dropwise to the reaction mixture via a syringe. Stir the reaction at −78° C. for 90 min. then allow to slowly warm to room temperature over 4 hr. Quench the reaction with saturated NaHCO3 solution. Dilute with more DCM, wash with more saturated NaHCO3 solution. Separate the organic layer, dry over anhydrous sodium sulfate, then evaporate the solvent under reduced pressure. Purify the residue by chromatography (silica gel, 6% 2M NH3-MeOH in DCM) to yield the desired 1-(6-bromo-pyridin-2-yl)-4-dimethylamino-cyclohexanol as a mixture of diastereomers (7.7 g, 67% yield): MS (ES): m/z=299 (M+H)+.

1. additionAfter the addition
2. customthe reaction at −78° C. for 1 hr
3. stirringStir
4. customthe reaction at −78° C. for 90 min.
5. temperatureto slowly warm to room temperature over 4 hr
6. customQuench
7. customthe reaction with saturated NaHCO3 solution
8. washwash with more saturated NaHCO3 solution
9. customSeparate the organic layer
10. dry with materialdry over anhydrous sodium sulfate
11. customevaporate the solvent under reduced pressure
12. customPurify the residue by chromatography (silica gel, 6% 2M NH3-MeOH in DCM)

ORD record

ord-5213da0838c64906816904f4a945b061

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07312236B2