Toluene → 1-Indanol

A 3-neck 500 mL round-bottomed flask fitted with a condenser and an addition funnel was charged with 2.62 g (0.11 mol) of Mg turnings and 20 mL of anhydrous diethyl ether. Slow addition of a solution of 25.10 g (0.09 mol) of 3,5-bis(trifluoromethyl) bromobenzene in diethyl ether (100 mL), followed by refluxing for 30 min, gave a brown-grey solution of the aryl Grignard reagent. The solution was cooled to room temperature (RT), filtered over a plug of Celite and evacuated to yield a brown oil. Toluene (40 mL) was added and the suspension cooled to 0° C. whereupon a solution of 2-indanone (9.22 g, 0.07 mol) in toluene (60 mL) was added dropwise to give a tan-brown slurry. This mixture was warmed to room temperature and stirred for an additional 3 hours. After cooling to 0° C. it was quenched with 150 mL of water, hexane (200 mL) added and the reaction mixture neutralized with 5 M HCl. The organic layer was separated, and the aqueous layer was extracted with two 50-mL portions of hexane. The combined organic layers were washed with two 50-mL portions of brine and dried over anhydrous magnesium sulfate. After filtration over Celite, the solvent was removed under vacuo yielding 21.5 g (89% based on 2-indanone) of 2-(bis-3,5-trifluoromethylphenyl) indanol as an off-white solid. 1H NMR (CDCl3, 23 C, 400 MHz): d 8.05 (s, 2H), 7.80 (s, 1H), 7.5-7.0 (M, 4H), 3.41 (m, 4H), 2.21 (s, 1H, OH). Under argon, this alcohol (21.5 g, 0.06 mol) and p-toluene-sulfonic acid monohydrate (800 mg) were dissolved in toluene (250 mL) and the solution was heated to reflux for 6 hours to afford 14.4 g, (70%) of 2-(bis-3,5(trifluoromethyl)-phenyl) indene upon recrystallization from diethyl ether/hexane at −18 C. 1H NMR (CDCl3, 23° C., 400 MHz): d 8.01 (s, 2H), Arf), 7.75 (s, 1H, Arf), 7.52 (d, J=7 Hz, 1H), 7.47 (d, J=7 Hz, 1H), 7.43 (s, 1H), 7.33 (dd, 2J=7 Hz, 1H), 7.27 (dd, 2J=7 Hz, 1H), 2.83 (s, 2H). 13C NMR (CDCl3, 23 C, 100 MHz): L144.3 (s), 143.1 (s), 138.0 (s), 132.1 (q, 2JC—F=33 Hz), 130.1 (d, JC—H=167 Hz), 127.0 (dd), JC—H=160 Hz, 2JC—H=7 Hz), 126.0 (dd, JC—H=159 Hz, 2JC—H=7 Hz)m 125.2 (brd, JC—H=162 Hz), 123.9 (dd, JC—H=156 Hz, 2JC—H=9 Hz), 123.4 (q, JC—F=273 Hz, CF3), 121.8 (dd, Jc-H=160 Hz, 2JC—H=8 Hz), 120.6 (brd, JC—H=167 Hz), 38.9 (td, JC—H=127 Hz, JC—H=7 Hz, CH2). C,H analysis: Anal. Found (Calcd): C, 62.45 (62-20); H 3.01 (3.07).

1. filtrationfiltered over a plug of Celite
2. customevacuated
3. customto yield a brown oil
4. additionwas added dropwise
5. customto give a tan-brown slurry
6. temperatureThis mixture was warmed to room temperature
7. temperatureAfter cooling to 0° C. it
8. customwas quenched with 150 mL of water, hexane (200 mL)
9. additionadded
10. customThe organic layer was separated
11. extractionthe aqueous layer was extracted with two 50-mL portions of hexane
12. washThe combined organic layers were washed with two 50-mL portions of brine
13. dry with materialdried over anhydrous magnesium sulfate
14. filtrationAfter filtration over Celite
15. customthe solvent was removed under vacuo

ORD record

ord-087b356df4c846bbba12168623db7e34

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06518378B2