Dichloromethane → 6-Hydroxy-2,3-dihydro-1H-indene-5-carbonitrile

To a stirred solution of Indan-5-ol (5.0 g, 32.3 mmol) in anhydrous dichloroethane (21.5 mL) was added, at 0° C., 1.0 M boron trichloride in dichloromethane (41.0 mL, 41.0 mmol, 1.2 eq), followed by methyl thiocyanate (2.43 mL, 35.5 mmol, 1.1 eq) and aluminum chloride (4.30 g, 2.3 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for 2 d and then cooled to 0° C. To the dark brown reaction mixture was added 50% aqueous sodium hydroxide solution (100 mL) until pH=11. The resulting yellow biphasic layers were stirred at reflux for 3 h. The biphasic layers were separated, and the aqueous layer was adjusted to pH=1 with 50% aqueous hydrogen chloride solution at 0° C. The acidified aqueous mixture was extracted with ethyl acetate, and the combined organic layers were dried over sodium sulfate and concentrated at reduced pressure. Crystallization from ether-hexane afforded the cyanophenol as a white solid (3.02 g, 50.9%). 1H-NMR (DMSO-d6) δ 10.67 (s,1H), 7.36 (s, 1H), 6.84 (s,1H), 2.81 (t, J=7.5 Hz, 2H), 2.73 (t, J=7.5 Hz, 2H), 1.99 to 1.93 (m, 2H); Rf=0.23, 25% ethyl acetate-hexane.

1. temperaturecooled to 0° C
2. stirringThe resulting yellow biphasic layers were stirred
3. temperatureat reflux for 3 h
4. customThe biphasic layers were separated
5. customwas adjusted to pH=1 with 50% aqueous hydrogen chloride solution at 0° C
6. extractionThe acidified aqueous mixture was extracted with ethyl acetate
7. dry with materialthe combined organic layers were dried over sodium sulfate
8. concentrationconcentrated at reduced pressure
9. customCrystallization from ether-hexane

ORD record

ord-f77ad4e70c754d40bdee1b1342638737

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07384947B2