Cesium carbonate → 5-Fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid ethyl ester

HRID 1827959Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of ethyl-2-chloro-5-fluoro-nicotinoate (50.4 g, 0.247 mol) (prepared according to the method of J. Med. Chem., 1993, 36(18), 2676–88, page 2684, column 2, 3rd example, ethyl-2-chloro-5-fluoropyridine-3-carboxylate) (29 g, 0.143 mol) and 3-methylsulphanyl-phenol (20 g, 0.143 mol) (prepared according to the method of WO 98/45268, page 68, preparation 61) in dioxane (300 mL) was treated with caesium carbonate (46.5 g, 0.143 mol) at room temperature. The reaction mixture was heated to 100° C. and stirred for 48 hours. The reaction mixture was concentrated in vacuo and the residue taken up in water (600 mL) and extracted with ethyl acetate (3×250 mL). The organics were combined, washed with brine (200 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5) to yield the title product as a yellow oil, 27.1 g (62%).

Workup

concentrationThe reaction mixture was concentrated in vacuo
extractionextracted with ethyl acetate (3×250 mL)
washwashed with brine (200 mL)
dry with materialdried over magnesium sulphate
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5)

Sources & evidence

ORD record: ord-b5af494f2acb4044a29929634a0e9a18
Source dataset: uspto-grants-2006_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07056934B2

Reaction notes

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