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 Ar was added NaH (60% in mineral oil, 0.48 g, 11.3 mmol). The reaction was heated to reflux for 1 h. The resulting orange colored suspension was cooled to 0° C. and 5-fluoro-2-methoxybenzaldehyde (1.54 g, 10.0 mmol) was added and the reaction was stirred for 12 h at room temperature. The mixture was poured to a separatory funnel containing ammonium chloride aqueous solution (sat. NH4Cl/H2O=1:1, v:v, 30 mL). The organics were extracted with EtOAc (3×80 mL) and the combined organic layers were washed with brine (60 mL) and dried over Na2SO4. The solvent was removed in vacuo and product was purified by flash column chromatography (Rf=0.15, EtOAc/Hexane, 7:93, v:v) to result in the product (2.63 g, 66%) as a mixture of cis and trans (cis:trans=4:1): 1H NMR (the 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), 3.90-3.87 (m, 2 H), 3.80 (s, 3 H), 2.64-2.62 (m, 2 H).

1. temperatureThe reaction was heated
2. temperatureto reflux for 1 h
3. additionThe mixture was poured to a separatory funnel
4. extractionThe organics were extracted with EtOAc (3×80 mL)
5. washthe combined organic layers were washed with brine (60 mL)
6. dry with materialdried over Na2SO4
7. customThe solvent was removed in vacuo and product
8. customwas purified by flash column chromatography (Rf=0.15, EtOAc/Hexane, 7:93, v:v)

ORD record

ord-e02906a09f574721b06e23e5ff44ba0f

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168635B2