18-Crown-6 → 3-Thiophen-3-yl-acrylic acid ethyl ester

Temperature

-78 °C

Potassium bis(trimethylsilyl)amide (3.92 g, 19.7 mol) was added to a solution of 18-Crown-6 (9.95 g, 37.6 mmol) and [Bis-(2,2,2 trifluoro-ethoxy)-phosphoryl]-acetic acid ethyl ester (6.54 g, 19.7 mmol) in dry THF (200 mL) at −78° C. After 30 minutes of stirring at this temperature, thiophene-3-carbaldehyde (2.0 g, 19.7 mmol) was added and the reaction was stirred for 3 hours at −78° C. after which the reaction was quenched with saturated ammonium chloride (200 mL). The reaction mixture was allowed to come to room temperature and was extracted with ethyl acetate (3×250 mL) and the combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL) and dried with MgSO4 Evaporation of the solvent in vacuo gave the crude product that was purified by silica-gel chromatography using a 0-40% ethylacetate-hexane gradient to afford the subtitle compound (2.7 g, 82.7%). MS calculated for C9H10O2S +H: 183, observed: 183; 1H NMR (300 MHz, CDCl3, ppm) 1.31 (t, J=7 Hz, 3H); 4.22 (q, J=7 Hz, 2H); 5.83 (d, J=13 Hz, 1H); 6.87 (d, J=7 Hz, 1H); 7.24-7.28 (m, 1H); 7.54 (dd, J1=5 Hz, J2=1 Hz, 1H); 8.07 (br d, J=3 Hz, 1H).

1. additionwas added
2. customwas quenched with saturated ammonium chloride (200 mL)
3. customto come to room temperature
4. extractionwas extracted with ethyl acetate (3×250 mL)
5. washthe combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL)
6. dry with materialdried with MgSO4 Evaporation of the solvent in vacuo
7. customgave the crude product that
8. customwas purified by silica-gel chromatography

ORD record

ord-5c079f21397645fc84e1cd556b1edba9

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07981919B2