Aniline → Ethyl 6-chloro-4-(phenylamino)nicotinate

HRID 2174233Notes

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

Participants

Conditions

Temperature: 80 °C

Procedure

Ethyl 4,6-dichloronicotinate (10.0 g, 45.44 mmol) in EtOH (100 mL) was stirred till a clear solution was obtained followed by addition of aniline (3.90 mL, 43.17 mmol) and 10 drops of conc. HCl. The resulting solution was heated to 80° C. for 2-3 h. The reaction mass was cooled to room temperature, poured onto ice-cold water and then extracted with EtOAc (3×250 mL). The combined organic phase was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude residue was then purified over silica gel (100-200 M, 2% EtOAc-hexane) to obtain the desired product ii (4.90 g, 39%). 1H-NMR (400 MHz, DMSO-d6): δ 9.72 (br s, 1H), 8.66 (s, 1H), 7.28-7.49 (m, 5H), 6.77 (s, 1H), 4.35 (q, J=7.20 Hz, 2H), 1.34 (t, J=7.20 Hz, 3H). [M+H]+ m/z=277.17.

Workup

customwas obtained
temperatureThe reaction mass was cooled to room temperature
additionpoured onto ice-cold water
extractionextracted with EtOAc (3×250 mL)
washThe combined organic phase was washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude residue was then purified over silica gel (100-200 M, 2% EtOAc-hexane)

Sources & evidence

ORD record: ord-c33eda35e80742b4afa317d8564e7446
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09060515B2

Reaction notes

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