Trimethyl orthoacetate as a convenient reagent for selective methylation of β-OH groups of (poly)hydroxynaphthazarins

Trimethyl orthoacetate was found to be a convenient reagent for methylation of the beta-OH groups of (poly)hydroxynaphthazarins. The substrates bearing one beta-OH group react with MeC(OMe)(3) to give the corresponding methoxy derivatives in 79-89% yields. Depending on the reaction conditions, methylation of substrates with two beta-OH groups on the different and the same rings affords either the corresponding mono-O-methylated (43-70%) or di-Omethylated (71-78%) derivatives. Trimethyl orthoacetate offers a good alternative to CH2N2 in the preparative synthesis of O-methylated (poly)hydroxynaphthazarin derivatives.