Hydrochloric Acid → 2-(Hydroxymethyl)benzo[b]thiophene

Temperature

-78 °C

Benzothiophene (5.0 g, 37.3 mmol) in anhydrous THF (100 ml) stirring at −20° C. was treated with n-butyllithium (34 ml, 1.6 M, 55.8 mmol) and stirred for 1 hour. The mixture was cooled to −78° C. and treated with paraformaldehyde (7.8 g, 261 mmol) in four portions. The mixture was allowed to slowly warm to room temperature with stirring overnight. The mixture was treated with 2N HCl (100 ml) and extracted with diethyl ether (2×100 ml). The organic phases were combined, dried over NaSO4, filtered, and the filtrate concentrated under reduced pressure. The residue was crystallized from DCM/hexanes to provide the title compound. 1H NMR (300 MHz, CDCl3) δ 4.94 (s, 2H) 7.23 (s, 1H) 7.33 (m, 3H) 7.74 (m, 1H); (ESI) m/z 165 (M+H)+.

1. temperatureto slowly warm to room temperature
2. stirringwith stirring overnight
3. extractionextracted with diethyl ether (2×100 ml)
4. dry with materialdried over NaSO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated under reduced pressure
7. customThe residue was crystallized from DCM/hexanes

ORD record

ord-99f40e3f94cb48bd8ff84d431f3f136f

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07235661B2