18-Crown-6 → HCID 69052122, compound

Temperature

-78 °C

To a solution of 18-crown-6 (9.1 g, 34.6 mmol) in 100 mL of THF at −78° C. was added bis(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phosphonate (4.13 g, 12.98 mmol). Potassium bis(trimethylsilyl)amide (19.6 mL of a 15 wt % solution in toluene, 12.98 mmol) was added dropwise over 20 min and the mixture was stirred an additional 1 h at −78° C. Then there was added isopropyl 2-formyl-6-(trifluoromethyl)benzoate (1.5 g, 5.74 mmol) in 10 mL of THF and the resulting cloudy mixture was stirred at −78° C. for 1 h. The reaction was quenched with sat'd aq NH4Cl, diluted with EtOAc, washed with brine, dried (MgSO4), filtered through a pad of silica gel and concentrated in vacuo. The residue was purified by flash chromatography (elution with 6:1 hexane/ethyl acetate) to afford 2.58 g (94%) of the title compound as an oil. 1H NMR (CDCl3): δ 7.66-7.62 (m, 2H), 7.51 (t, 1H, J=7.7 Hz), 7.11 (d, 1H, J=12.1 Hz), 6.11 (d, 1H, J=12.1 Hz), 5.26 (septet, 1H), 3.63 (s, 3H), 1.32 (d, 6H, J=6.0 Hz). LRMS (ESI): 339.19 (M+H+Na)+.

1. stirringthe resulting cloudy mixture was stirred at −78° C. for 1 h
2. customThe reaction was quenched with sat'd aq NH4Cl
3. additiondiluted with EtOAc
4. washwashed with brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered through a pad of silica gel
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography (elution with 6:1 hexane/ethyl acetate)

ORD record

ord-c50688e368514940a289a0396aa5c4e6

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572805B2