1-Chloro-2-fluoro-4-methoxybenzene

CLEAR COLOURLESS LIQUID

4-chloro-3-fluorophenol (500 mg, 3.41 mmol) in acetone (10 mL) was added potassium carbonate (942.59 mg, 6.82 mmol) and iodomethane (1.94 g, 13.64 mmol). The reaction mixture was stirred at 60 deg.C for 16 hours. TLC (petroleum ether: ethyl acetate = 20: 1) showed the reaction was complete. The mixture was concentrated to remove the solvent, to the residue was added water (20 mL) and (20mL × 3) and extracted with ethyl acetate. The organic layer was dried and concentrated to give the title compound (470 mg, 2.93 mmol, 85.84percent yield) as a colorless oil.Example 32 l-(5-Chloro-4-fluoro-2-methoxyphenyl)ethanone; [0355] To a stirred solution of DMF (10 mL) and 4-chloro-3-fluorophenol (1 g, 6.84 mmol) at RT, K CO3 (1.4 g, 10.3 mmol) was added and solution was allowed to stir at room temperature for additional 15 min. Methyl iodide (1.16 g, 8.21 mmol) was added to the mixture and mixture was allowed to stir for overnight at RT. After the completion of reaction 10 mL of water was added and was extracted with ethyl acetate (3X15 mL) and the resulting organic layer was washed with water, brine and dried. l-chloro-2-fluoro-4-methoxybenzene was obtained via column chromatography (10/1 Hexanes/Ethyl acetate). To a stirred solution of l -chloro-2-fluoro-4-methoxybenzene (1.09 g, 6.82 mmol) and AICI3 (1.36 g, 10.23 mmol) in CHTo a solution of 2, 2, 6, 6-tetramethylpipe dine (528 mg, 3.74 mmol) in Tetrahydrofuran (10 ml.) was added n-butyllithium in hexane(1 .5ml, 3.74 mmol) at -78 C. After completion of the addition the reaction mixture was stirred at -78 C for 1 h. Then, 1 -chloro-2-fluoro-4- methoxybenzene (200 mg, 1 .246 mmol) was added and the mixture was stirred for another 1 h. Acetaldehyde (274 mg, 6.23 mmol) was then added and the mixture was stirred for another 1 h. The reaction was quenched with saturated NH4CI (10ml_) and was extrated with EtOAc (2x10 ml_). T combined organic layers were dried over Na2S04 and concentrated, m/z: [M - OH]+ Calcd for C9H9CIFO 187.0; Found 187

Molecular Weight:160.57
XLogP3:2.6
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:160.0091207
Monoisotopic Mass:160.0091207
Topological Polar Surface Area:9.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes