Sodium hydride → 2-Chloro-4-(oxetan-3-yloxy)pyrimidine

To a suspension of oxetan-3-ol (100 mg, 1.35 mmol) in tetrahydrofuran (1 mL) and N,N-dimethylformamide (1 mL) was added 60% sodium hydride in mineral oil (81 mg, 2.03 mmol). The mixture was stirred for 30 minutes at room temperature. The reaction was then cooled to 0° C. and a solution of 2,4-dichloropyrimidine (300 mg, 2.03 mmol) in tetrahydrofuran (1 mL) and N,N′-dimethylformamide (1 mL) was added. The mixture was warmed to room temperature and stirred for 24 h. The reaction was then diluted with ethyl acetate (20 mL) and washed with 1:1 water:brine (3×40 mL). The organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by Chromatography on silica gel (10-60% ethyl acetate in hexanes) to afford 2-chloro-4-(oxetan-3-yloxy)pyrimidine (91 mg, 0.49 mmol, 36% yield) as a white solid. MS ESI: [M+H]+ m/z 186.8.

1. temperatureThe reaction was then cooled to 0° C.
2. temperatureThe mixture was warmed to room temperature
3. stirringstirred for 24 h
4. washwashed with 1:1 water
5. dry with materialThe organic extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe resulting residue was purified by Chromatography on silica gel (10-60% ethyl acetate in hexanes)

ORD record

ord-de77907801884e85a925340ab91193fd

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759366B2