5-Chloro-2-methylpyridine → 4-(5-Chloro-2-pyridyl)-3(S)-phenyl-2(R)-butanol

To a solution of 5-chloro-2-methylpyridine (Step A, 1.1 g, 8.7 mmol) in 15 mL anhydrous ether was added phenyl lithium (1.8 M in cyclohexane/ether, 7.2 mL, 13 mmol) at 0° C., and the reaction was stirred at room temperature for 30 min. The resulting mixture was cooled back to 0° C., and was added (1R,2R)-1-phenylpropylene oxide (2.3 g, 17 mmol), and the reaction was allowed to warm to room temperature overnight. The reaction mixture was partitioned between EtOAc (100 mL) and water (100 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (2×100 mL). The combined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated to dryness, and the residue was purified by flash column chromatography on silica gel eluted with 10 to 40% EtOAc in hexane to afford the title compound. 1H NMR (500 MHz, CD3OD): δ 8.28 (d, 1H), 7.59 (dd, 1H), 7.25-7.12 (m, 5H), 7.05 (d, 1H), 4.03 (m, 1H), 3.29 (dd, 1H), 3.19 (dd, 1H), 3.12 (m, 1H), 1.12 (d, 3H).

1. temperatureThe resulting mixture was cooled back to 0° C.
2. temperatureto warm to room temperature overnight
3. customThe reaction mixture was partitioned between EtOAc (100 mL) and water (100 mL)
4. customThe organic layer was separated
5. extractionthe aqueous layer extracted with EtOAc (2×100 mL)
6. dry with materialThe combined organic extracts were dried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated to dryness
9. customthe residue was purified by flash column chromatography on silica gel
10. washeluted with 10 to 40% EtOAc in hexane

ORD record

ord-2b919d17c4ed4a929caba4c6b6d2b9ad

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07550489B2