Acetic Acid → 4-tert-Butyl-2-chloropyrimidine

Temperature

0 °C

To a dry flask containing 2-chloropyrimidine (1.0 g, 8.7 mmol) was added anhydrous Et2O (8.7 mL) and the solution was cooled to −30° C. tBuLi (1.7 M solution in n-pentane, 5.7 mL, 9.6 mmol) was added dropwise and the reaction was held at −30° C. for 30 min. The reaction was warmed to 0° C. and stirred at that temperature for 30 min, at which time the reaction was quenched by dropwise addition of a solution of acetic acid (0.60 mL, 10.5 mmol) in THF (3 mL) and water (1 mL). The reaction was maintained at 0° C. and a solution of DDQ (2.38 g, 10.5 mmol) in THF (8.7 mL) was added. After 15 minutes, NaOH (1 M, 1 mL) and water (10 mL) were added, and the dark reaction mixture was transferred to a separatory funnel containing EtOAc (50 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted once with EtOAc (50 mL). The combined organic phases were washed with saturated aqueous sodium chloride (50 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Adsorption of the oily black residue on silica, followed by chromatography on silica using a gradient solvent system of 5→30% EtOAc/hexanes furnished 4-tert-butyl-2-chloropyrimidine (1.00 g, 67%) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) δ 8.49 (d, J=5.2, 1H), 7.24 (d, J=5.2, 1H), 1.33 (s, 9H).

1. additionwas added dropwise
2. temperatureThe reaction was maintained at 0° C.
3. waitAfter 15 minutes
4. customthe dark reaction mixture
5. customwas transferred to a separatory funnel
6. customThe layers were separated
7. extractionthe aqueous layer was extracted once with EtOAc (50 mL)
8. washThe combined organic phases were washed with saturated aqueous sodium chloride (50 mL)
9. dry with materialdried over anhydrous MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure

ORD record

ord-4d1920a0f444481e82950c7a1a307cb3

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759366B2