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

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.

1. customThe ice bath was removed
2. temperatureThe reaction was cooled to 0° C. in an ice bath
3. stirringThe resulting clear yellow solution was stirred for 2 h at room temperature and 3 h
4. temperatureat reflux
5. temperatureAfter cooling to room temperature the mixture
6. concentrationwas concentrated
7. washwashed with water (3×50 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a colorless liquid

ORD record

ord-27749fa23d45438eae80718ba85e5ad7

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129398B2