Methanol → Methyl 2-cyclobutyl-5-iodo-4-methylbenzoate

Temperature

0 °C

To a solution methyl 2-cyclobutyl-4-methylbenzoate (compound 89.2, 4.77 g, 23.3 mmol) in concentrated sulfuric acid (100 mL) at 0° C., was added N-iodosuccinimide (5.25 g, 23.3 mmol) portion-wise. The mixture was stirred at 0° C. for 30 min and then at RT for 2 hours. The thick, dark mixture was cooled back to 0° C., then MeOH (100 mL) was added slowly and carefully. The mixture was heated at 60° C. for 2 hours. After cooling to room temperature, the volatile solvents were removed under reduced pressure and the residue was carefully poured onto ice water (200 mL). The mixture was extracted with EtOAc (2×) and the combined organic extracts were washed with brine, aqueous NaHCO3 (1 M), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1) to yield 5.0 g (65%) of the title compound as a clear oil. 1H NMR (400 MHz, Chloroform-d) δ 8.19 (s, 1H), 7.24 (s, 1H), 4.17-4.04 (m, 1H), 3.86 (s, 3H), 2.48-2.44 (s, 3H), 2.40-2.28 (m, 2H), 2.13-1.92 (m, 3H), 1.85-1.75 (m, 1H).

1. waitat RT for 2 hours
2. temperatureThe thick, dark mixture was cooled back to 0° C.
3. temperatureThe mixture was heated at 60° C. for 2 hours
4. temperatureAfter cooling to room temperature
5. customthe volatile solvents were removed under reduced pressure
6. additionthe residue was carefully poured onto ice water (200 mL)
7. extractionThe mixture was extracted with EtOAc (2×)
8. washthe combined organic extracts were washed with brine, aqueous NaHCO3 (1 M)
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1)

ORD record

ord-4ba9e9633b0e4c36ba0f11e2f206a491

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2