Isopropyl iodide → HCID 13400966, compound

Participants

Reaction Steps

A mixture of 4-bromo-2,6-dimethylphenol (4.69 g, 23.3 mmol), 2-iodo-propane (15.81 g, 93.0 mmol) in isopropanol (200 mL) and 1 N aq. NaOH (50 mL) is stirred at rt for 24 h. The mixture is diluted with diethyl ether, washed with 1 N aq. HCl and 1 N aq. NaOH, dried over Na2SO4, filtered and concentrated to give crude 5-bromo-2-isopropoxy-1,3-dimethyl-benzene (4.62 g) as an orange oil; LC-MS: tR=1.07 min. The arylbromide is dissolved in THF (100 mL) and cooled to −78° C. BuLi (15 mL of a 1.6 N solution in hexane) is slowly added (30 min) and the mixture is stirred at −78° C. for 30 min. The mixture is transferred via needle to a cooled (0° C.) solution of dimethylcarbonate (10.7 g, 118.8 mmol) in THF (50 mL). The mixture is stirred for 15 h, quenched with 3 N aq. LiOH (100 mL) and stirred at 60° C. for 24 h. The mixture is diluted with ether (200 mL) and 1M aq. NaOH (100 mL), the phases separated and the org. phase re-extracted with NaOH (50 mL). The aq. phases are washed with diethyl ether (2×50 mL), carefully acidified to pH 3 with 25% HCl. The org. phases are discarded. The aq. phase is extracted with DCM (5×75 mL). The org. extracts are dried over Na2SO4, filtered and evaporated to give 4-isopropoxy-3,5-dimethyl-benzoic acid (2.23 g) as a beige solid; LC-MS: tR=0.91 min, [M+1]+=209.07, 1H NMR (CDCl3): δ 1.34 (d, J=6.3 Hz, 6H), 2.34 (s, 6H), 4.32 (hept, J=6.0 Hz, 1H), 7.81 (s, 2H).

Provenance & Evidence