Dimethylformamide → 4-(Benzyloxy)-2-(2-chloroethyl)tetrahydrofuran

Participants

Reaction Steps

To an ice-cold stirred solution of oxalyl chloride (1.005 mL, 11.48 mmol) in CH2Cl2 (30 mL) was added DMF (0.914 mL, 11.80 mmol), dropwise, over 10 min. The ice bath was removed and the white slurry stirred for 30 min at room temperature. The reaction was cooled to 0° C. in an ice bath and a solution of 2-(4-(benzyloxy)tetrahydrofuran-2-yl)ethanol (2.3847 g, 10.73 mmol) in CH2Cl2 (30 mL) was rapidly added via cannula. The resulting clear yellow solution was stirred for 2 h at room temperature and 3 h at reflux. After cooling to room temperature the mixture was concentrated and the resulting yellow residue taken up in Et2O (100 mL), washed with water (3×50 mL) followed by brine (25 mL), then dried (MgSO4), filtered and concentrated to give a colorless liquid. Flash column chromatography on a silica gel column using 9:1 hexane/ethyl acetate provided 4-(benzyloxy)-2-(2-chloroethyl)tetrahydrofuran (2.47 g, 10.26 mmol, 96% yield) as a colorless oil. 1H NMR (500 MHz, CDCl3) δ: 7.27-7.37 (5 H, m), 4.48 (1.6 H, s), 4.41 (0.4 H, s), 4.17-4.23 (1 H, m), 3.96-4.11 (2 H, m), 3.72 (0.8 H, dd, J=10.1, 4.9 Hz), 3.59-3.70 (2.2 H, m), 2.30 (0.8 H, dt, J=13.4, 7.0 Hz), 2.09-2.25 (1.2 H, m), 1.89-2.01 (1 H, m), 1.69-1.74 (0.8 H, m), 1.57-1.64 (0.2 H, m). LCMS (M+H) calcd for C13H18ClO3: 241.1; found: 241.05.

Provenance & Evidence