Cesium carbonate → Ethyl 2-[3-(ethylsulfanyl)phenoxy]-5-fluoronicotinate

HRID 724284Notes

Reaction equation

Cl[C:2]1[N:12]=[CH:11][C:10]([F:13])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH2:14]([S:16][C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1)[CH3:15].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[CH2:7]([O:6][C:4](=[O:5])[C:3]1[CH:9]=[C:10]([F:13])[CH:11]=[N:12][C:2]=1[O:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([S:16][CH2:14][CH3:15])[CH:18]=1)[CH3:8]

Participants

Conditions

Temperature: 100 °C

Procedure

Ethyl 2-chloro-5-fluoro-nicotinate (J. Med. Chem. 1993, 36, 2676, M. Winn et. al.) (5.0 g, 24 mmol), 3-ethylsulfanylphenol (3.8 g, 24 mmol) and caesium carbonate (7.98 g, 24 mmol) were suspended in dioxan (50 ml) and the reaction was heated to 100° C. and stirred at this temperature under nitrogen for 8 h. The reaction was cooled to room temperature, filtered and the solid washed with ethyl acetate (50 ml). The filtrate was concentrated under reduced pressure, and the residue was purified by flash column chromatography on silica gel eluting with cyclohexane:ethyl acetate (95:5) to give 5-fluoro-2-(3-ethylsulfanyl-phenoxy)-nicotinic acid ethyl ester (1.16 g).

Workup

temperatureThe reaction was cooled to room temperature
filtrationfiltered
washthe solid washed with ethyl acetate (50 ml)
concentrationThe filtrate was concentrated under reduced pressure
customthe residue was purified by flash column chromatography on silica gel eluting with cyclohexane:ethyl acetate (95:5)

Sources & evidence

ORD record: ord-2a1db452f43a4da3b881fa7b3b936d8a
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07141586B2

Reaction notes

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