2-Amino-5-fluoro-N-methoxy-N-methylbenzamide → (2-Amino-5-fluorophenyl)(phenyl)methanone

Temperature

-78 °C

To a −78° C. solution of 2-amino-5-fluoro-N-methoxy-N-methylbenzamide in THF (100 mL) was added 1M phenylmagnesium bromide in THF (124.12 mL, 124.12 mmol). The reaction was stirred from −78° C. to ambient temperature over 3.5 h and then cooled again to −78° C. Additional 1M phenylmagnesium bromide in THF (62.06 mL, 62.06 mmol) was added and the reaction stirred at −78° C. for another hour. The reaction was then diluted with CH2Cl2 (500 mL) and quenched with saturated ammonium chloride solution (300 mL). The layers were separated and the organic one washed with brine (300 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by normal phase chromatography (3-8% MeOH/CH2Cl2) yielded (2-amino-5-fluorophenyl)(phenyl)methanone as a yellow solid. 1H NMR (CDCl3, 400 MHz) 7.63 (m, 2H, ArH); 7.55 (m, 1H, ArH); 7.47 (m, 2H, ArH); 7.15 (m, 1H, ArH); 7.08 (m, 1H, ArH); 6.70 (m, 1H, ArH); 5.91 (s, NH2); MS (Electrospray): m/z 216.1 (M+H).

1. stirringthe reaction stirred at −78° C. for another hour
2. customquenched with saturated ammonium chloride solution (300 mL)
3. customThe layers were separated
4. washthe organic one washed with brine (300 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification by normal phase chromatography (3-8% MeOH/CH2Cl2)

ORD record

ord-ab87011a7b994501bcc359bba50fa0ce

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07745452B2