Isopropanol → Isopropyl 1-(3-fluoro-2-pyridyl)-3-(isopropoxymethyl)pyrazole-4-carboxylate
Reaction equation
Br[CH2:2][C:3]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]([C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[N:4]=1.[CH3:20][CH:21]([CH3:23])[O-:22].[Li+].[Li].[CH3:26]C(O)C>>[F:19][C:18]1[C:13]([N:5]2[CH:6]=[C:7]([C:8]([O:10][CH:11]([CH3:26])[CH3:12])=[O:9])[C:3]([CH2:2][O:22][CH:21]([CH3:23])[CH3:20])=[N:4]2)=[N:14][CH:15]=[CH:16][CH:17]=1Participants
5
Procedure
To a solution of ethyl 3-(bromomethyl)-1-(3-fluoro-2-pyridyl)pyrazole-4-carboxylate (1.5 g, 4.57 mmol), in propan-2-ol (23 mL), lithium isopropoxide (3.02 g) is added and the mixture is stirred overnight at room temperature. After that time more lithium isoproxide (4.5 g) is added in three portions of 1.5 g each every 16 hours. After the last addition, the reaction mixture is finally stirred at 40° C. for 16 hours. Solvent is evaporated and the residue dissolved in ethyl acetate and washed with brine. Organic layer is decanted and dried over sodium sulfate. Solvent is evaporated and the residue is purified by normal phase Isco chromatography using as eluent dichloromethane and methanol to give 317 mg of isopropyl 1-(3-fluoro-2-pyridyl)-3-(isopropoxymethyl)pyrazole-4-carboxylate. MS (m/z): 322 (M+1).