Imidazole → 4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propoxy)benzoic acid

Participants

Reaction Steps

To a solution of 1 (10.0 g, 0.05 mmol) and tert-butyldimethylsilyl chloride (17.50 g, 0.11 mmol 1) in anhydrous N,N-dimethylformamide (45 mL) was quickly added imidazole (14.16 g, 0.21 mmol) under argon. After stirring overnight, the reaction mixture was shaken with diethyl ether (100 mL) and water (300 mL). The ether layer was separated and washed with a saturated NaHCO3 solution (100 mL×2) before drying over anhydrous MgSO4. The solvent was evaporated, and the solid residue was purified by flash column chromatography on silica gel with methylene chloride: hexanes (1:1) as the eluent to afford 2 with silyl-protected hydroxyl and carboxyl groups. This compound was dissolved in tetrahydrofuran: methanol (50 mL: 150 mL) followed by stirring with a solution of K2CO3 (5 g, 36.18 mmol) in water (50 mL) for 1 h. The volume of the solution was reduced by 75% via evaporation under reduced pressure. Brine (150 mL; 120 g NaCl in 500 mL H2O) was added to the resultant slurry, and the pH was adjusted to 5.0 with a 1 M KHSO4 solution. The precipitate was collected by filtration and washed with water before drying under vacuum at 60° C. to yield 2 (13.7 g, 87%). 1H NMR (200 MHz, CDCl3): δ 0.06 (s, 6H, —S1—CH3), δ 0.91 (s, 9H,-SiCCH3)δ 2.01 (quintet, 2H, —CH2—), δ 3.81 (t, 2H, —CH2OAr), δ 4.16 (t, 2 H, HOCH2—), δ 6.96 (d, 2H, aromatic ring), δ 8.06 (d, 2H, aromatic ring).

Provenance & Evidence