Ethyl 4-iodobenzoate → Ethyl 4-cyclopropylbenzoate

Temperature

-70 °C

Indium trichloride (2.2 g, 10 mmol) and THF (50 mL) were combined under nitrogen and cooled to −70° C. Cyclopropylmagnesium bromide solution (33 mL, 30 mmol, 0.92M) was added dropwise while maintaining the reaction temperature ≦−60° C. After the addition was complete the reaction was stirred 0.5 h with cooling then 0.5 h with the cooling bath removed. The resulting solution was added via cannula to a refluxing solution of ethyl-4-iodobenzoate (5.5 g, 20 mmol), trans-dichlorobis(triphenylphosphine)palladium(II) (421 mg, 0.60 mmol) and THF (100 mL) under nitrogen. After 24 h, the contents of the reaction flask were cooled and the solvent was removed in vactio. Water (100 mL) and 5% KHSO4 were added and the mixture was extracted with CH2Cl2 (3×100 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and filtered. The filtrate was removed in vacuo and the remaining residue was purified by flash column chromatography (hexane:EtOAc 95:5) to give the 4-cyclopropyl-benzoic acid ethyl ester as an orange oil.

1. temperaturewhile maintaining the reaction temperature ≦−60° C
2. additionAfter the addition
3. temperaturewith cooling
4. custom0.5 h with the cooling bath removed
5. waitAfter 24 h
6. temperaturethe contents of the reaction flask were cooled
7. customthe solvent was removed in vactio
8. additionWater (100 mL) and 5% KHSO4 were added
9. extractionthe mixture was extracted with CH2Cl2 (3×100 mL)
10. washThe combined organic extracts were washed with brine
11. dry with materialdried with Na2SO4
12. filtrationfiltered
13. customThe filtrate was removed in vacuo
14. customthe remaining residue was purified by flash column chromatography (hexane:EtOAc 95:5)

ORD record

ord-e4974b044fd14df0b8ee40973ca991f3

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07259157B2