4-Fluoro-N-methoxy-N-methylbenzamide → HCID 118023371, compound

Temperature

-78 °C

To a solution of tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (50 g, 146.2 mmol) in anhydrous THF (700 mL) was dropwise added n-BuLi (2.5 M in hexane, 70 mL, 175 mmol) at −78° C. under nitrogen. The mixture was stirred at −78° C. for 1 h, followed by the addition of a solution of 4-fluoro-N-methoxy-N-methylbenzamide (30 g, 163.9 mmol) in anhydrous THF (100 mL). After stirred at −78° C. for another 2 h, the reaction mixture was quenched with saturated aqueous NH4Cl (250 mL) and extracted with ethyl acetate (200 mL*3). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was diluted with propan-2-ol (150 mL) and stirred at RT for 30 mins. The solid was collected via filtration, washed with propan-2-ol (100 mL) and petroleum ether (300 mL), and dried under vacuum to give the title compound (26 g, yield 46%) as a yellow solid. MS (ES+) C20H23FN4O3 requires: 386. found 331 [M−56+H]+; purity: 100% (UV214).

1. customat −78° C.
2. stirringAfter stirred at −78° C. for another 2 h
3. customthe reaction mixture was quenched with saturated aqueous NH4Cl (250 mL)
4. extractionextracted with ethyl acetate (200 mL*3)
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. additionThe residue was diluted with propan-2-ol (150 mL)
9. stirringstirred at RT for 30 mins
10. filtrationThe solid was collected via filtration
11. washwashed with propan-2-ol (100 mL) and petroleum ether (300 mL)
12. customdried under vacuum

ORD record

ord-d032aeb32a76438d86de361eba897831

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200002B2