4-Fluorophenol → HCID 11333485, compound

Temperature

80 °C

To a stirred suspension of NaH (0.57 g, 23.86 mmol) in DMF (5 mL), a solution of (2S,5S)-5-ethynyl-2-(p-toluene sulfonyloxymethyl)-tetrahydrofuran 17 (3.34 g, 11.92 mmol) in DMF (5 mL) was added, followed by the addition of 4fluoro phenol (1.74 g, 15.5 mmol) in DMF (5 mL) and heating at 80° C. for 2 hours. The reaction mixture was cooled to room temperature and treated with NH4Cl solution (20 mL). It was extracted with ether (3×40 mL) and organic layer was washed with water (2×25 ML), brine (25 mL) and dried (Na2SO4). Evaporation of solvent and purification of residue by column chromatography (Si-gel, 2% EtOAc-hexane) afforded (2S,5S)-5-ethynyl-2-(4-fluorophenoxymethyl)-tetrahydrofuran 18 (1.55 g) in 59.6% yield as a colorless liquid, whose spectral data was comparable with the reported reference values. [α]D−15.07(c 1.26, CHCl3); 1HNMR (CDCl3, 200 MHz): δ2.0-2.35 (m, 4H, H-3,4′), 2.45 (d, 1H, J 2.2 Hz, H-7), 3.95 (dd, 1H, J 4.5, 9.0 Hz, H-1), 4.12 (dd, 1H, J 4.54, 9.0 Hz, H-1a), 4.35 (quin, 1H, H-2), 4.65 (m, 1H, H-5), 6.85-7.05 (m, 4H, Ar—H); 13CNMR (CDCl3, 50 MHz): δ28.24, 33.1, 68.45, 72.9, 79.9, 83.8, 71.28, 115.43, 115.52, 115.68, 115.89, 154.91, 159.66; MS: m/z 220 (M+); HRMS: Calculated for C13H13O2 (M+): 220.089958; Observed; 220.089905.

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionIt was extracted with ether (3×40 mL) and organic layer
3. washwas washed with water (2×25 ML), brine (25 mL)
4. dry with materialdried (Na2SO4)
5. customEvaporation of solvent and purification of residue by column chromatography (Si-gel, 2% EtOAc-hexane)

ORD record

ord-2fdee42bad9647cebef9f9070875f10f

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06541647B2