Sodium hydride → (R)-4-((1,4-Dioxan-2-yl)methoxy)-5-bromo-2-chloropyrimidine

To a solution of (S)-(1,4-dioxan-2-yl)methanol (185 mg, 1.6 mmol) in anhydrous THF (2 mL), was added NaH (60% oil dispersion, 42 mg, 1.04 mmol). The mixture was stirred at room temperature for 2.5 h. The reaction mixture was cooled to −20° C. and 5-bromo-2,4-dichloropyrimidine (252 mg, 1.04 mmol) was added at once. The resulting mixture was stirred between −15° C. and 15° C. for 6 h and quenched with water. The aqueous solution was extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified on ISCO (hexane/ethyl acetate gradient, 5-20%) to give the title compound (57 mg, 17.7%) as colorless oil. 1HNMR (CDCl3, 400 MHz): 8.44 (s, 1H), 4.47 (dd, J1=5.5 Hz, J2=11.7 Hz, 1H), 4.43 (dd, J1=4.5 Hz, J2=11.7 Hz, 1H), 3.98-4.04 (m, 1H), 3.72-3.91 (m, 4H), 3.61-3.69 (m, 1H), 3.55 (dd, J1=10.0 Hz, J2=11.5 Hz, 1H). MS (ESI) m/z: Found: 309.0 (M1+1); Calc. 308.0 (M+)

1. temperatureThe reaction mixture was cooled to −20° C.
2. stirringThe resulting mixture was stirred between −15° C. and 15° C. for 6 h
3. customquenched with water
4. extractionThe aqueous solution was extracted with ethyl acetate (3×10 mL)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified on ISCO (hexane/ethyl acetate gradient, 5-20%)

ORD record

ord-370bc16356764438a53d983df73b3438

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513242B2