N,N,N',N'-Tetramethylethylenediamine → 2-Hydroxy-2-(2,3,4-trimethoxyphenyl)cyclohexanone

Participants

Reaction Steps

A stirred solution of 8.70 g (51.8 mmol) of 1,2,3-trimethoxybenzene and 8.25 mL (54.7 mmol) of tetramethylethylenediamine in 40 mL of THF was cooled in an ice bath and 24.0 mL of 2.5 molar n-BuLi in hexanes (60.0 mmol) was added dropwise over 20 min. The cooling bath was removed and the mixture was stirred at room temperature for 2 h. The mixture was cooled to -70° C. and a solution of 6.95 g (49.6 mmol) of 2-ethoxycyclohex-2-en-1-one in 30 mL of THF was added dropwise over 45 min. The cooling bath was removed and the mixture was stirred at room temperature for 2 days. The mixture was poured into 150 mL of 5% aqueous HCl and allowed to stand for 2 h. The mixture was extracted with two 80 mL portions of ether. The combined ether extracts were washed with 50 mL of saturated aqueous NaHCO3, and dried over MgSO4. Removal of the solvent left 13.56 g of an oil which was purified by flash chromatography on a column of 100 g of silica gel eluted successively with 250 mL portions of 0, 8, 16, 24, 40, 60, 80 and 100% ether in hexanes to furnish 7.08 g of 2-hydroxy-2-(2,3,4-trimethoxyphenyl)cyclohexanone as a solid, mp 88°-91° C. 1H-NMR (CDCl3) d 1.5-1.8 (4H), 2.0 (m, 1H), 2.5 (m, 2H), 2.9 (m, 1H), 3.7 (s, 3H), 3.88 (s, 3H), 3.92 (s, 3H), 4.6 (s, 1H), 6.75 (d, 1H), 7.25 (d, 1H).

Provenance & Evidence