Isopropyl iodide → Methyl 3-chloro-4-isopropoxybenzoate

Temperature

60 °C

To methyl 3-chloro-4-hydroxy-benzoate (3.0 g, 16.1 mmol) in DMF (19 mL) was added potassium carbonate (8.9 g, 64.3 mmol) followed by 2-iodopropane (5.5 g, 3.2 mL, 32.2 mmol). The reaction mixture was heated at 60° C. for 1.5 hours. The reaction mixture was cooled, filtered and diluted with EtOAc and the solvent was concentrated in vacuo. The material was dissolved in EtOAc and washed with water (3×10 mL) and brine (1×10 mL). The organic layer was dried over Na2SO4, filtered and the solvent was removed in vacuo to give methyl 3-chloro-4-isopropoxybenzoate. To the ester was added dioxane (47 mL) and sodium hydroxide (42.7 mL of 1 M, 42.7 mmol) and the reaction was heated at 80° C. for 15 minutes. The reaction was cooled and solvent was removed in vacuo. The resulting residue was dissolved in water and washed with EtOAc (3×10 mL) and the layers were separated. The aqueous layer was acidified to pH 1 and was extracted with EtOAc (3×10 mL). The organic layer was separated and dried over Na2SO4, filtered and the solvent was removed in vacuo to yield 3-chloro-4-isopropoxy-benzoic acid (2.86 g, 83%) as a white solid. ESI-MS m/z calc. 213.6. Found 215.3 (M+1)+; Retention time: 1.51 minutes (3 min run). 1H NMR (400.0 MHz, CDCl3) δ 8.05 (d, J=2.2 Hz, 1H), 7.90-7.87 (dd, J=8.8, 2.2H, 1H), 7.06 (d, J=8.8 Hz, 1H) and 3.90 (s, 3H) ppm.

1. temperatureThe reaction mixture was cooled
2. filtrationfiltered
3. additiondiluted with EtOAc
4. concentrationthe solvent was concentrated in vacuo
5. dissolutionThe material was dissolved in EtOAc
6. washwashed with water (3×10 mL) and brine (1×10 mL)
7. dry with materialThe organic layer was dried over Na2SO4
8. filtrationfiltered
9. customthe solvent was removed in vacuo

ORD record

ord-6e332e47b83f48f586381408e9c86e14

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08828996B2