4-Fluoroaniline → Methyl 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

HRID 15510

반응식

HRID 15510 반응식
O=[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][O:3]1.[F:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1>CN(C=O)C>[F:12][C:13]1[CH:19]=[CH:18][C:16]([N:17]2[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[C:2]2=[O:3])=[CH:15][CH:14]=1

참가 물질

4

반응물 2

HCID 97314-FluoroanilineHCID 117704Methyl 2-oxo-2H-pyran-3-carboxylate

생성물 1

HCID 21081723Methyl 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of methyl 2-oxo-2H-pyran-3-carboxylate (10.0 g, 65 mmol, Aldrich) in DMF (80 mL) at ice bath temperature was added a solid of 4-fluoroaniline (7.21 g, 65 mmol), stirred for 15 min. and the reaction mixture was warmed to rt, stirred for 3 h at rt. To the 4-fluoroaniline adduct intermediate formed via Michael addition was added in situ solids of EDCI.HCl (14.8 g, 77 mmol) and DMAP (1.80 g) at rt. The reaction mixture was stirred at rt overnight. Most of DMF was removed in vacuo, and to the residue were added 1N aq HCl (150 mL) and EtOAc (400 mL), the EtOAc layer was separated, and the aqueous layer was washed with EtOAc (2×200 mL), the combined EtOAc layer was washed with brine (150 mL), dried over MgSO4 and concentrated in vacuo. The residue was triturated with iPrOH (180 mL) to obtain the 1st crop of product (8.5 g) as a yellow solid. The mother liquor was concentrated, and the residue was triturated with a small amount of ether to obtain the 2nd crop of product (2.5 g, total 11 g, 68%). 1H NMR (CDCl3) δ 8.23 (dd, 1H, J=7.2, 2.2 Hz), 7.57 (dd, 1H, J=6.6, 1.7 Hz), 7.32-7.34 (m, 2H), 7.17 (t, 2H, J=8.8 Hz), 6.32 (t, 1H, J=7.1 Hz), 3.89 (s, 3H); MS(ESI+) m/z 248.2 (M+H)+.

후처리

  1. stirringstirred for 3 h at rt

출처 및 근거

ORD 기록
ord-9e675692a0304dd7bd6adf8acfeb59ff
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732613B2

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