4-Hydroxybenzaldehyde → 4-(Pyrrolidin-1-ylmethyl)phenol

Participants

Reaction Steps

NaB(OAc)3H (43.4 g, 0.21 mol) was added in portions during 30 min to a mixture of pyrrolidine (17 mL, 0.21 mol) and 4-hydroxybenzaldehyde 1 (20 g, 0.16 mol) in CH2Cl2 (200 mL) under vigorous stirring and cooling with an ice bath in an atmosphere of argon. The mixture was stirred for 3 h and cooled. Then 10 N NaOH (20.5 mL) and water (300 mL) were added. The organic layer was separated, the aqueous one was extracted with chloroform (3×200 mL). The organic fractions were evaporated. The residue was dissolved in water, concentrated HCl (15 mL) was added, and the mixture was extracted with ether (3×200 mL). The organic fractions were discarded. The aqueous layer was alkalized with 10 N NaOH (16 mL) and extracted with CH2Cl2 (3×200 mL). The combined extracts were washed with brine, dried with Na2SO4, and evaporated. The title compound (16.6 g, 57%) was obtained as yellow crystals. 1H NMR-data (DMSO-d6): 9.18 (br.s, 1H, OH); 7.00 (d, 2H, Ph, J=8.6 Hz); 6.68 (d, 2H, Ph, J=8.6 Hz); 3.43 (s, 2H, CH2); 2.33-2.42 (m, 4H); 1.62-1.71 (m, 4H).

Provenance & Evidence