Pyridine → 4-(Benzyloxy)tetrahydrofuran-2-yl acetate

Temperature

-78 °C

To a stirred solution of 4-(benzyloxy)dihydrofuran-2(3H)-one (3.15 g, 16.39 mmol) in CH2Cl2 (100 mL) was added, dropwise, 1M DIBAL-H/toluene (2.56 g, 18.03 mmol) over 10 min at −78° C. After 2 h, pyridine (3.98 mL, 49.2 mmol), solid 4-(dimethylamino)pyridine (DMAP) (2.202 g, 18.03 mmol) and Ac2O (6.19 mL, 65.6 mmol) were added and the solution was stirred for 6 h at −78° C. and slowly warmed to room temperature overnight (15 h). The resulting orange reaction mixture was stirred with sat. NH4Cl (50 mL) for 30 min. The organic layer was separated and washed with 1N aq. NaHSO4 (3×50 mL). The combined aq. layers were extracted with CH2Cl2 (2×50 mL) and the combined CH2Cl2 layers washed with 1N aq. NaHSO4 (50 mL), sat. NaHCO3 (50 mL) followed by brine (50 mL), then dried (Na2SO4), filtered and concentrated to afford a yellow oil. Flash column chromatography on a silica gel column using 15-30% ethyl acetate/hexane provided 4-(benzyloxy)tetrahydrofuran-2-yl acetate (3.5769 g, 15.14 mmol, 92% yield) as a clear oil. 1H NMR (500 MHz, CDCl3) δ: 7.26-7.39 (5 H, m), 6.41 (0.3 H, dd, J=5.7, 2.0 Hz), 6.24-6.30 (0.7 H, dd, J=4.9, 1.8 Hz), 4.46-4.58 (2 H, m), 4.32-4.37 (0.3 H, m), 4.22-4.28 (0.7 H, m), 4.00-4.10 (2 H, m), 2.15-2.38 (2 H, m), 2.07 (3 H, s). LCMS (M-C2H30) calcd for C13H16O4: 177.09; found: 177.0.

1. temperatureslowly warmed to room temperature overnight (15 h)
2. customThe organic layer was separated
3. washwashed with 1N aq. NaHSO4 (3×50 mL)
4. extractionThe combined aq. layers were extracted with CH2Cl2 (2×50 mL)
5. washthe combined CH2Cl2 layers washed with 1N aq. NaHSO4 (50 mL), sat. NaHCO3 (50 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a yellow oil

ORD record

ord-5f5448ba54974fef8518de30bd4c4907

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129398B2