Sodium hydride → HCID 86623857, compound

Temperature

0 °C

To a suspension of 2-(1,3-dioxolan-2-yl)ethyltriphenylphosphonium bromide (5.0 g, 11.3 mmol) in THF (30 mL) under an atmosphere of Ar was added NaH (60% in mineral oil, 0.48 g, 11.3 mmol) and the mixture obtained was heated to reflux for 1 h. The orange suspension obtained was cooled to 0° C. and 5-fluoro-2-methoxybenzaldehyde (1.54 g, 10.0 mmol) was added and the reaction was warmed to room temperature and continued with stirring for 12 h. The reaction mixture was poured to a separatory funnel containing ammonium chloride aqueous solution (sat. NH4Cl/H2O 50:50, v:v, 50 mL). The organics were extracted with EtOAc (3×80 mL) and the combined organic layers were washed with brine (60 mL) and dried over sodium sulfate. The solvent was then removed in vacuo and the crude product obtained was purified by flash column chromatography (EtOAc/hexane, 7:93, v:v, Rf=0.15) to give the product (2.63 g, 66%) as a 4:1 mixture of cis and trans diastereomers: 1H NMR (major isomer): (CDCl3, 500 MHz): δ 7.08 (dd, J=3.1, 8.7 Hz, 1 H), 6.93 (dt, J=3.1, 8.7 Hz, 1 H), 6.78 (dd, J=4.3, 8.7 Hz, 1 H), 6.63 (d, J=11.9 Hz, 1 H), 5.83 (td, J=7.3 Hz, 11.9 Hz, 1 H), 4.99 (t, J=4.6 Hz, 1 H), 4.02-3.99 (m, 2 H), 3.9-3.87 (m, 2 H), 3.8 (s, 3 H), 2.64-2.62 (m, 2 H).

1. customthe mixture obtained
2. temperaturewas heated
3. temperatureto reflux for 1 h
4. customThe orange suspension obtained
5. temperaturethe reaction was warmed to room temperature
6. additionThe reaction mixture was poured to a separatory funnel
7. extractionThe organics were extracted with EtOAc (3×80 mL)
8. washthe combined organic layers were washed with brine (60 mL)
9. dry with materialdried over sodium sulfate
10. customThe solvent was then removed in vacuo
11. customthe crude product obtained
12. customwas purified by flash column chromatography (EtOAc/hexane, 7:93, v:v, Rf=0.15)

ORD record

ord-fdd1238c72f14b1ebdcb1911187a9b78

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168635B2