2-Fluoro-4-iodoaniline → Ethyl 6-chloro-4-(2-fluoro-4-iodoanilino)nicotinate

HRID 917690Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([Cl:13])[CH:3]=1.[F:14][C:15]1[CH:21]=[C:20]([I:22])[CH:19]=[CH:18][C:16]=1[NH2:17]>CCO.Cl>[Cl:13][C:4]1[CH:3]=[C:2]([NH:17][C:16]2[CH:18]=[CH:19][C:20]([I:22])=[CH:21][C:15]=2[F:14])[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Ethyl 4,6-dichloronicotinate [prepared according to the literature procedure of J. Chem. Soc. 5163 (1963)] (4.00 g, 18.2 mmol) and 2-fluoro-4-iodoaniline (4.30 g, 18.2 mmol) were dissolved in EtOH (80 mL), to which was added conc. HCl (6 drops). This mixture was heated, in an oil bath at 90° C., for 15 h. The solution was allowed to cool, then refrigerated whereupon the desired product crystallised out of solution as fine needles. The product was isolated by filtration and washed with 10% Et2O/hexanes to give ethyl 6-chloro-4-(2-fluoro-4-iodoanilino)nicotinate as white needles (3.79 g, 50%), m.p. (EtOAc/n-hexane) 162-164° C. 1H NMR [(CD3)2SO, 400 MHz] δ 9.62 (s, 1H), 8.69 (s, 1H), 7.82 (dd, J=9.9, 1.9 Hz, 1H), 7.61-7.66 (m, 1H), 7.33 (t, J=8.5 Hz, 1H), 6.67 (d, J=1.8 Hz, 1H), 4.37 (q, J=7.1 Hz, 2H), 1.35 (t, J=7.1 Hz, 3H). Anal. Calcd for C14H11ClFIN2O2: C, 40.0; H, 2.6; N, 6.7. Found: C, 40.3; H, 2.2; N, 6.7.

Workup

temperatureto cool

Sources & evidence

ORD record: ord-cada7e5ba37d4a28afbfb3e7eb34baf7
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07273877B2

Reaction notes

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