O-methylation of p-tert-butylcalix[6]arene with methyl p-tosylate in acetonitrile under limiting conditions of base and electrophile has been investigated, which led to isolation of all twelve O-methylated derivatives from the reaction mixture. Previously unreported direct single step syntheses of (1,2,4-tri)-, (1,2,3,4-tetra)-and (1,2,3,5-tetra)-O-methylated derivatives from p-tert-butylcalix[6]arene have been achieved in this study and are reported here for the first time.