Imidazole → 4-Bromo-6-((tert-butyldimethylsilyloxy) methyl)-2-methylpyrimidine

To an ice cold solution of (6-bromo-2-methylpyrimidin-4-yl)methanol (4.10 g, 20.2 mmol, Preparation #4) in DMF (40 mL) were added imidazole (5.50 g, 80.8 mmol, Spectrochem) and TBDMS-Cl (6.10 g, 40.4 mmol, Spectrochem). The resulting reaction mixture was warmed to RT and stirred about 5 h. The mixture was diluted with ice cold water (200 mL), the product was extracted with diethyl ether (3×200 mL) and washed with water (1×100 mL) and brine solution (1×150 mL). The organic layer was dried over sodium sulphate and concentrated in vacuum. The resulting crude material was purified by silica gel chromatography using 10 to 20% of EtOAc in hexane as the eluent. Relevant fractions containing the target compound were combined and evaporated to dryness under reduced pressure to afford 4-bromo-6-((tert-butyldimethylsilyloxy) methyl)-2-methylpyrimidine 5.9 g (93%). 1H NMR (400 MHz, CDCl3) δ: 7.54 (s, 1H), 4.72 (s, 2H), 2.67 (s, 3H), 0.96 (s, 9H), 0.13 (s, 6H); MS m/z: 319.2 (M+H)+.

1. customThe resulting reaction mixture
2. extractionthe product was extracted with diethyl ether (3×200 mL)
3. washwashed with water (1×100 mL) and brine solution (1×150 mL)
4. dry with materialThe organic layer was dried over sodium sulphate
5. concentrationconcentrated in vacuum
6. customThe resulting crude material was purified by silica gel chromatography
7. additionRelevant fractions containing the target compound
8. customevaporated to dryness under reduced pressure

ORD record

ord-c271e231e1474f5a937cc911b9e8f8dd

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029409B2