* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference:
[1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1976, vol. 30, p. 141 - 149
2
[ 342-52-9 ]
[ 59255-94-6 ]
Reference:
[1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1976, vol. 30, p. 141 - 149
3
[ 342-52-9 ]
[ 17809-36-8 ]
Yield
Reaction Conditions
Operation in experiment
74%
at 50℃; for 2 h;
3g (0.0151mol) of 52 N-(2-fluoro-6-nitrophenyl)acetamide (3a) are dissolved in 30ml of 53 concentrated H2SO4 and brought to 50°C for 2h. After cooling, the solution is poured into an ice bath and an abundant precipitate is observed. After filtration, the acidic aqueus solution is extracted with diethyl ether. The pure 9 compound is obtained through flash chromatography. Yield 74percent. M.P. 47–48°C. 1H NMR (DMSO‑d6): δ 7.82 (d, 1H, J=8.8MHz, H-5), 7.42 (m, 1H, H-3), 7.25 (s, 2H, NH2), 6.63 (m, 1H, H-4). GC/MS: 157 (M+H). Anal. Calcd for (C6H5FN2O2): C, 46.16; H, 3.23; F, 12.17; N, 17.94. Found: C, 46.18; H, 3.27; F, 12.15; N, 17.98.
Reference:
[1] European Journal of Medicinal Chemistry, 2019, vol. 161, p. 399 - 415
[2] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1976, vol. 30, p. 141 - 149
4
[ 342-52-9 ]
[ 124-41-4 ]
[ 17809-36-8 ]
Reference:
[1] Recueil des Travaux Chimiques des Pays-Bas, 1949, vol. 68, p. 88,89
3g (0.0151mol) of 52 N-(2-fluoro-6-nitrophenyl)acetamide (3a) are dissolved in 30ml of 53 concentrated H2SO4 and brought to 50C for 2h. After cooling, the solution is poured into an ice bath and an abundant precipitate is observed. After filtration, the acidic aqueus solution is extracted with diethyl ether. The pure 9 compound is obtained through flash chromatography. Yield 74%. M.P. 47-48C. 1H NMR (DMSO-d6): delta 7.82 (d, 1H, J=8.8MHz, H-5), 7.42 (m, 1H, H-3), 7.25 (s, 2H, NH2), 6.63 (m, 1H, H-4). GC/MS: 157 (M+H). Anal. Calcd for (C6H5FN2O2): C, 46.16; H, 3.23; F, 12.17; N, 17.94. Found: C, 46.18; H, 3.27; F, 12.15; N, 17.98.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 24.25h;
Step iN-(2-fluoro-6-nitrophenyl)acetamide A mixture of 2-Fluoro-6-nitroaniline (12.6g, 80.8 mmol) and DIPEA (13.5g, 1.3eq) in DCM (150 mL) was treated with acetyl chloride (8.2g, 1.3eq) dropwise over 15 mins and stirred at room temperature for 24 hrs. The reaction mixture was quenched by addition of H20, the organic layer was collected and the aqueous phase re-extracted with DCM, the combined organics were washed with dil. HCl(aq), brine, dried (phase separator) and concentrated in vacuo to afford a yellow solid (yield 15.6g, 90%). LCMS method A, (ES+) 199, RT = 1.33 min
90%
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 39h;
Step i N-(2-fluoro-6-nitrophenyl)acetamide A mixture of 2-Fluoro-6-nitroaniline (12.6 g, 80.8 mmol) and DIPEA (13.5 g, 1.3 eq) in DCM (150 mL) was treated with acetyl chloride (8.2 g, 1.3 eq) dropwise over 15 mins and stirred at room temperature for 24 hrs. The reaction mixture was quenched by addition of H2O, the organic layer was collected and the aqueous phase re-extracted with DCM, the combined organics were washed with dil. HCl(aq), brine, dried (phase separator) and concentrated in vacuo to afford a yellow solid (yield 15.6 g, 90%). LCMS method A, (ES+) 199, RT=1.33 min.
90%
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 24.25h;
A mixture of 2-Fluoro-6-nitroaniline (12.6 g, 80.8 mmol) and DIPEA (13.5 g, 1.3 eq) in DCM (150 mL) was treated with acetyl chloride (8.2 g, 1.3 eq) dropwise over 15 mins and stirred at room temperature for 24 hrs. The reaction mixture was quenched by addition of H2O, the organic layer was collected and the aqueous phase re-extracted with DCM, the combined organics were washed with dil. HCl (aq), brine, dried (phase separator) and concentrated in vacuo to afford a yellow solid (yield 15.6 g, 90%). LCMS method A, (ES+) 199, RT=1.33 min.
With hydrogenchloride; tin(II) chloride dihdyrate; In ethanol; water; at 20℃;
General procedure: The respective nitrobenzene derivative (1 eq) was dissolved in EtOH and concentrated hydrochloric acid (each 1 ml/mmol) before slowly adding a suspension of tinn(II) chloride dihydrate (4-5 eq) in concentrated hydrochloric acid (~1-1.5 ml/mmol). After stirring at room temperature for 2-5 h, the reaction mixture was basified to a pH of 9 with 6 N sodium hydroxide solution and the formed precipitate was filtered. The filtrate was then extracted with DCM (3×). The organic phases were combined, washed with brine, dried over anhydrous sodium sulfate and filtered. DCM was removed under reduced pressure. The crude solid was purified by column chromatography (DCM/MeOH, 95:5).