Chlorotrimethylsilane → Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoate

To a stirred solution of 5.32 g of 2-fluoro-5-iodobenzoic acid from Preparation No. 28 in 20 mL of THF, under argon, is added 3.9 g of carbonyldiimidazole. In a separate flask, 2.8 mL of chlorotrimethylsilane is added to a mixture of 3.74 g of potassium ethyl malonate in 20 mL of acetonitrile. The mixture is stirred under argon for 18 h, then cooled to 0° C. for the dropwise addition of 6.6 mL of DBU. The mixture is stirred for 3 h at 0° C., then the solution of acyl imidazolide prepared above is added via cannula. After 2 h, the mixture is partitioned between ether and excess dilute HCl, and the organic phase is washed with dilute HCl and brine and dried (MgSO4). Removal of the solvent under reduced pressure left a colorless oil, which is flash chromatographed on silica using 10% ethyl acetate in hexane to provide 5.07 g of the title compound as dense pinkish prisms.

1. stirringThe mixture is stirred for 3 h at 0° C.
2. additionabove is added via cannula
3. waitAfter 2 h
4. customthe mixture is partitioned between ether and excess dilute HCl
5. washthe organic phase is washed with dilute HCl and brine
6. dry with materialdried (MgSO4)
7. customRemoval of the solvent under reduced pressure
8. waitleft a colorless oil, which
9. customchromatographed on silica using 10% ethyl acetate in hexane

ORD record

ord-e294f4fbfa9e4ac6b5f303e0542a3dcb

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06248739B1