Iodine → Ethyl 2-iodo-5-(4-methoxyphenyl)oxazole-4-carboxylate

Temperature

-78 °C

To a solution of ethyl 5-(4-methoxyphenyl)oxazole-4-carboxylate (2.75 g, 11.1 mmol) in anhydrous THF (20 mL) under an N2 atmosphere at −78° C. was added 1M lithium bis(trimethylsilyl)amide in THF (18 mL, 18 mmol), dropwise. The reaction mixture was stirred at −78° C. for one hour. A solution of iodine (5.0 g, 19.7 mmol) in anhydrous THF (10 mL) was added dropwise and the reaction stirred at −78° C. for a further 1 hour. The mixture was then warmed to −10° C. and 10% sodium thiosulfate solution and EtOAc was added. The aqueous phase was extracted with EtOAc and the combined organic phase was washed with brine, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by silica gel column chromatography using a 10-40% EtOAc in hexanes gradient to afford ethyl 2-iodo-5-(4-methoxyphenyl)oxazole-4-carboxylate (3.33 g, 8.9 mmol, 80%) as a white solid. 1H NMR (CDCl3) 1.40 (3H, t), 3.87 (3H, s), 4.41 (2H, q), 6.98 (2H, d), 8.01 (2H, d). LCMS (1) Rt: 2.13 min; m/z (ES+) 374.

1. stirringthe reaction stirred at −78° C. for a further 1 hour
2. temperatureThe mixture was then warmed to −10° C.
3. extractionThe aqueous phase was extracted with EtOAc
4. washthe combined organic phase was washed with brine
5. dry with materialdried over MgSO4
6. customthe solvent removed in vacuo
7. customThe residue was purified by silica gel column chromatography

ORD record

ord-bc4b557e90704c3aa7567cae7d57a8e3

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378095B2