Diisopropylamine → Methyl 5-(2,5-Dichlorophenyl)pentanoate

Participants

Reaction Conditions

Reaction Steps

Diisopropylamine (841 μl, 6 mmol) was added to 20 ml of tetrahydrofuran under nitrogen atmosphere and cooled to 0° C. 5.5 ml of 2.5N n-butyllithium (13 mmol) was added and the reaction was stirred for 20 minutes. The reaction was then cooled to -78° C. 2,5-Dichlorotoluene (642 ul, 5 mmol) was added and stirring was continued for 2 hours at -78° C. Trimethyl 4-bromoorthobutyrate (1.14 g, 5 mmol) was added to the reaction mixture in 10 ml tetrahydrofuran. The reaction was stirred for 5 minutes at -78° C., allowed to come to room temperature and stirred overnight. The reaction was worked-up by adding 10 ml of saturated KH2PO4, removal of most of the tetrahydrofuran on a rotary evaporator followed by partitioning of the aqueous residue between ethyl acetate and 1N HCl. The organic phase was washed twice with 1N HCl, once with 5% sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated to a residue. Flash chromatography (silica gel; hexane/toluene (39/1)) of the residue gave 1.10 g (84%; GC retention time=15.8 minutes) of a water white oil. 1H NMR (300 MHz, CDCl3) delta=7.24 (d, J=8.5 Hz, H3), 7.18 (d, J=2.5 Hz, H6), 7.09 (dd, J=2.5, 8.5 Hz, H4), 3.66 (s, --COOCH3), 2.69 (t, J=7.8 Hz, Ar--CH2 --), 2.35 (t, J=7.0 Hz, --CH2 --COO--), 1.70-1.55 (m, --CH2 --CH--CH2 --CH2 --).

Provenance & Evidence