Reaction #325947

Reaction equation

4-fluoro-3-methoxybenzaldehyde

benzyl magnesium chloride

→

1-(4-fluoro-3-methoxyphenyl)-2-phenylethanol

Yield 60.2%

Solvents

THF

THF

Conditions

Workup

1. 1
   Temperatureto cool to rt
2. 2
   Otherquenched by addition of sat. NH4Cl
3. 3
   ExtractionThe reaction mixture was extracted with EtOAc (3×)
4. 4
   Washthe combined organic layers were washed with sat. NaCl
5. 5
   Dryingdried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   OtherThe residue was purified by flash chromatography (SiO2, eluting with 0-40% EtOAc/hexane)

Procedure

To a solution of 4-fluoro-3-methoxybenzaldehyde (25 g, 162 mmol) in THF (150 mL) was added a solution of benzyl magnesium chloride (2 M solution in THF, 122 mL, 243 mmol) in THF (50 mL). The reaction mixture was heated at 50° C. for 2 h. The reaction mixture was allowed to cool to rt and quenched by addition of sat. NH4Cl. The reaction mixture was extracted with EtOAc (3×) and the combined organic layers were washed with sat. NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2, eluting with 0-40% EtOAc/hexane) to yield 1-(4-fluoro-3-methoxyphenyl)-2-phenylethanol as a yellow oil (24 g, 60% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.27-7.32 (m, 2H), 7.21-7.27 (m, 1H), 7.16 (d, J=7 Hz, 2H), 7.01 (dd, J=11, 8 Hz, 1H), 6.92 (dd, J=8, 2 Hz, 1H), 6.82 (ddd, J=8, 4, 1 Hz, 1H), 4.80-4.88 (m, 1H), 4.66 (d, J=6 Hz, 1H), 3.84 (s, 3H), 2.91-3.04 (m, 2H).

Source