Ethyl (2-oxo-cyclohex-3-enyl)acetate → Ethyl [4-(4-fluorophenyl)-2-oxo-cyclohexyl]acetate

Reaction equation

[O:1]=[C:2]1[CH:7]=[CH:6][CH2:5][CH2:4][CH:3]1[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].[F:14][C:15]1[CH:20]=[CH:19][C:18]([Mg]Br)=[CH:17][CH:16]=1>CSC.O1CCCC1>[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH:6]2[CH2:5][CH2:4][CH:3]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:2](=[O:1])[CH2:7]2)=[CH:17][CH:16]=1

Participants

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).