toluene-4-sulfonic acid in methanol T=22°C;

1: rac-6-[(tetrahydro-2H-pyran-2-yl)oxy]-1-hexyne With n-butyllithium in tetrahydrofuran; hexane T=-78°C; Substitution; 1 h; 2: 2-(4-bromobutoxy)tetrahydro-2H-pyran in tetrahydrofuran; N,N,N',N',N'',N''-hexamethylphosphoric triamide; hexane T=20°C; Substitution; 4 h; Further stages.;

1.1: 98 percent / p-TsOH / CH2Cl2 / 4 h / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 2.2: 84 percent / tetrahydrofuran; hexane; hexamethylphosphoric acid triamide / 4 h / 20 °C View Scheme

1: 1.) n-BuLi, 2.) HMPA / 1) THF, -78 deg -> 0 deg C within 30 min, 2) -78 deg, 12h 2: 96 percent / p-TsOH / methanol / 22 °C View Scheme

1: 1) n-BuLi, 2) 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / 1) THF, hexane, -10 deg C, 0.5h. 2a) -10 deg C, 0.5h, 2b) RT, 1h 2: 550 mg / Bu4NF / tetrahydrofuran / 48 h / Ambient temperature View Scheme