4-bromo-3-methyl-2,3-dihydro-1H-inden-1-one synthesis

Yield:102539-53-7 101 g (86%)

Reaction Conditions:

with potassium hydroxide;thionyl chloride;sodium ethanolate;AlCl₃ in ethanol;dichloromethane;water;

Steps:

20 4-Bromo-3-methylindan-1-one

4-Bromo-3-methylindan-1-one To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2*200 ml of cold water, and dried in air. The dibasic acid obtained was then decarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl₂ was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl₂ was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl₃ in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm³ of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3*300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K₂CO₃ and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). Anal. calc. for C₁₀H₉BrO: C, 53.36; H, 4.03. Found: C, 53.48; H, 3.90. ¹H NMR (CDCl₃): δ 7.75 (dd, J=7.8 Hz, J=0.6 Hz, 1H, 7-H), 7.68 (dd, J=7.5 Hz, J=0.6 Hz, 1H, 5-H), 7.26 (t, J=7.6 Hz, 1H, 6-H), 3.48-3.58 (m, 1H, 3-H), 2.96 (dd, J=19.0 Hz, J=7.8 Hz, 1H, 2-H), 2.39 (dd, J=19.0 Hz, J=1.6 Hz, 1H, 2'-H), 2.43 (d, J=7.1 Hz, 3H, 2-CH₃). ¹³C NMR (CDCl₃): δ 205.4, 158.3, 138.3, 129.3, 122.6, 121.4, 109.6, 45.6, 34.0, 20.6.

References:

US2007/135595,2007,A1