Reaction #40889

Reaction equation

ester

ethyl (2-oxo-cyclohex-3-enyl)acetate

4-fluorophenylmagnesium bromide

→

ethyl [4-(4-fluorophenyl)-2-oxo-cyclohexyl]acetate

Solvents

dimethyl sulfide

tetrahydrofuran

Conditions

Workup

1. 1
   Otherdid not rise above −40° C
2. 2
   OtherReaction
3. 3
   Otherbefore quenching with 1N HCl (300 ml)
4. 4
   Extractionextracting the products with ether (3×300 ml)
5. 5
   WashCombined organic phase washed with saturated sodium chloride
6. 6
   Dryingdried over magnesium sulfate
7. 7
   Otherevaporated to dryness
8. 8
   OtherThe crude oil was purified by silica chromatography
9. 9
   Washeluting with hexane-ethyl acetate mixtures (10-20%)

Procedure

This ester (4 g, 0.022 mmol), copper (I) bromide-dimethyl sulfide complex (4.88 g, 0.023 mmol) in dimethyl sulfide (20 ml) and tetrahydrofuran (120 ml) was cooled to −40° C. under nitrogen and treated dropwise with 4-fluorophenylmagnesium bromide (1M solution in THF, 43.9 ml) so that the temperature did not rise above −40° C. Reaction was stirred for 20 minutes before quenching with 1N HCl (300 ml) and extracting the products with ether (3×300 ml). Combined organic phase washed with saturated sodium chloride, dried over magnesium sulfate and evaporated to dryness. The crude oil was purified by silica chromatography eluting with hexane-ethyl acetate mixtures (10-20%), to give ethyl [4-(4-fluorophenyl)-2-oxo-cyclohexyl]acetate as a colourless oil, 2.8 g. 1H NMR δ (ppm) (CDCl3): 7.26-7.11 (2H, m), 7.04-6.94 (2H, m), 4.18-4.11 (2H, m), 3.55-3.44 (1H, m), 3.00-2.90 (1H, m), 2.80-2.73 (2H, m), 2.69-2.55 (1H, m), 2.28-2.17 (2H, m), 2.10-1.88 (2H, m), 1.61-1.42 (1H, m) and 1.31-1.25 (3H, m).

Source