Phenol → 2-[(3,4-Dimethoxyphenyl)ethynyl]-4,5-dimethoxy-1-(methoxymethoxy)-benzene

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 5 (3.13 g, 9.60 mmol, 1.0 equiv) in CH2Cl2 (380 mL under Ar at 25° C. was treated with Na2HPO4 (3.27 g, 23.03 mmol, 2.4 equiv) and m-CPBA (3.98 g, 11.52 mmol, 1.2 equiv). After 18 h, the mixture was diluted with saturated aqueous NaHCO3, extracted with EtOAc, washed with saturated aqueous NaHCO3 and saturated aqueous NaCl, dried (Na2SO4), and concentrated under reduced pressure. The formate was redissolved in MeOH (120 mL), treated with 10% aqueous KOH (7.8 mL, 15.6 mmol, 1.6 equiv), and the mixture was stirred at 25° C. for 1.5 h. The reaction was quenched with the addition of 10% aqueous HCl, extracted with CH2Cl2, washed with H2O, dried (Na2SO4), and the solvent was removed under reduced pressure. An analytically pure sample of the phenol could be prepared by chromatography (SiO2, 5% EtOAc/CH2Cl2): mp 164-165° C. (EtOAc-hexanes); MALDIHRMS (DHB) m/z 337.1058 (M+Na+, C18H18O5 requires 337.1046). A solution of the crude phenol in CH2Cl2 (100 mL) under Ar at 0° C. was treated with iPr2NEt (6.70 mL, 38.4 mmol, 4.0 equiv) and chloromethyl methyl ether (2.19 mL, 28.8 mmol, 3.0 equiv). The mixture was warmed to 25° C. and allowed to stir for 18 h. Following dilution with H2O, the mixture was extracted with CH2Cl2, washed with saturated aqueous NaHCO3, saturated aqueous NaCl, dried (Na2SO4), and concentrated under reduced pressure. Chromatography (SiO2, 4.5 (15 cm, 5% EtOAc/CH2Cl2) afforded 6 (2.32 g, 67% yield) as an orange solid: mp 84-86° C. (EtOAc-hexanes); MALDIHRMS (DHB) m/z 358.1411 (M+, C20H22O6 requires 358.1416).

Provenance & Evidence