Trifluoroacetic acid → Methyl 5-iodo-4-isopropyl-2-methylbenzoate

Temperature

0 °C

To methyl 4-isopropyl-2-methylbenzoate (compound 198.1, 2.31 g, 12.0 mmol, 1.0 equiv) in a 100 mL round bottom flask was carefully added TFA (24 mL) and the mixture was cooled to 0° C. N-Iodosuccinimide (2.70 g, 12.0 mmol, 1.0 equi) was added portionwise over 2 minutes and the resulting mixture was added under nitrogen and stirred at 0° C. for 20 min then at room temperature for 15 hours. The mixture was carefully diluted. To a mixture of dichloromethane (50 mL) and added to saturated aqueous disodium phosphate to maintain a pH above 3 (total disodium phosphate about 500 mL). The mixture was shaken well, separated and the aqueous was extracted with additional DCM (5×25 mL). The combined organics was washed with a mix of saturated sodium sulfite (10 mL) plus water (40 mL) followed by brine (50 mL), dried (Na2SO4), filtered and removed in vacuo. The crude product was purified by silica column chromatography (hexanes to 3% ethyl acetate) to obtain the title compound as a light tan oil (3.59 g, 94%). 1H NMR (400 MHz, CDCl3): δ 8.35 (s, 1H), 7.08 (s, 1H), 3.87 (s, 3H), 3.17 (septet, J=6.8 Hz, 1H), 2.59 (s, 3H), 1.23 (d, J=6.8 Hz, 6H).

1. additionthe resulting mixture was added under nitrogen
2. waitat room temperature for 15 hours
3. additionThe mixture was carefully diluted
4. stirringThe mixture was shaken well
5. customseparated
6. extractionthe aqueous was extracted with additional DCM (5×25 mL)
7. washThe combined organics was washed with
8. additiona mix of saturated sodium sulfite (10 mL) plus water (40 mL)
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. customremoved in vacuo
12. customThe crude product was purified by silica column chromatography (hexanes to 3% ethyl acetate)

ORD record

ord-2a6a06f6070542ecae51b789a4f0d3a3

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2