4-Fluorobenzyl chloride → 4-[2-(4-Fluoro-phenyl)-1,1-dimethoxy-ethyl]-pyridine
Reaction equation
C([Li])CCC.[CH3:6][O:7][CH:8]([O:15][CH3:16])[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1.[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.[Cl-].[NH4+]>CCCCCC.O1CCCC1>[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][C:8]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)([O:15][CH3:16])[O:7][CH3:6])=[CH:20][CH:19]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
315 mL of n-butyllithium 1.6 M solution in hexane is added dropwise to a solution of 70.3 g (0.46 mole) of 4-dimethoxymethyl-pyridine in 1.4 L of tetrahydrofuran under nitrogen at −70° C. After 30 min. at −70° C., 73 g (0.505 mole) of 4-fluorobenzyl chloride in 280 mL of tetrahydrofuran is added dropwise. After 10 more min. at −70° C., the reaction mixture is allowed to reach room temperature and then stirred for 30 further min. The reaction mixture is poured into 2 L ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed with water and dried over magnesium sulfate. After concentration the residue is purified by chromatography on silica gel (ethylacetate/hexane 1/1) to give 114 g of 4-[2-(4-Fluoro-phenyl)-1,1-dimethoxy-ethyl]-pyridine as yellow oil.
Workup
- customat −70° C.
- customto reach room temperature
- extractionextracted with ethyl acetate
- washThe organic phase is washed with water
- dry with materialdried over magnesium sulfate
- concentrationAfter concentration the residue
- customis purified by chromatography on silica gel (ethylacetate/hexane 1/1)
Sources & evidence
- ORD record
- ord-5c983e7399a649d69d87e3adb06b90bd
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08084395B2
Reaction notes
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