Imidazole → 3-Imidazol-1-yl-2,2-dimethyl-indan-1-one

Temperature

-78 °C

To a solution of trifluoromethansulfonic anhydride (1.13 mL, 6.75 mmol) in dichloromethane (10 mL) at −78° C. is added, via cannula, a solution of diisopropylethylamine (1.8 mL, 10.1 mmol) and 3-hydroxy-2,2-dimethyl-indan-1-one, prepared as described in Example 20, (400 mg, 2.25 mmol) in dichloromethane (5 mL). The reaction is stirred at −78° C. for 10 minutes and then is placed at −10° C. for 10 minutes. The reaction is then re-cooled to −78° C. and a solution of imidazole (920 mg, 13.5 mmol) in dichloromethane (12 mL) is added via cannula. The reaction is then placed at room temperature for 1 hour, at which time it is diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the aqueous layer is extracted two times with ethyl acetate. The combined organic layers are dried with MgSO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 1:3 to 1:0), to afford 3-imidazol-1-yl-2,2-dimethyl-indan-1-one; MS: (ESI) m/z 227 (M+H)+; 1H NMR: (400 MHz, CDCl3) δ ppm 0.80 (s, 3 H), 1.41 (s, 3 H), 5.52 (s, 1 H), 6.73 (s, 1 H), 7.12 (s, 1 H), 7.51 (d, J=7.6 Hz, 1 H), 7.56 (s, 1 H), 7.62 (t, J=7.5 Hz, 1 H), 7.70-7.80 (m, 1 H), 7.91 (d, J=7.6 Hz, 1 H).

1. waitis placed at −10° C. for 10 minutes
2. temperatureThe reaction is then re-cooled to −78° C.
3. waitThe reaction is then placed at room temperature for 1 hour, at which time it
4. customThe layers are separated
5. extractionthe aqueous layer is extracted two times with ethyl acetate
6. dry with materialThe combined organic layers are dried with MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 1:3 to 1:0)

ORD record

ord-65c210704e4d4bff922d46d1af3fd77a

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436035B2