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 4-fluoro phenol (1.74 g, 15.5 mmol) in DMF (5 mL) and heating at 80° C. for 2hours. 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 δ 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): δ 28.24, 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-9902c5331e844677901c1bc71697ac7c

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06310221B1