tert-Butanol → 3,5-Dimethyl-1-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine

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Reaction Steps

1-(4-Chloro-[1,2,5]thiadiazol-3-yl)-3,5-dimethyl-piperazine (7.9 g, 34 mmol), pyridinyl-methanol (7.7 g, 70 mmol), potassium tert-butyl butoxide (11.4 g, 101 mmol) and tert-butyl alcohol (100 mL) were combined and stirred at room temperature overnight. The reaction mixture is diluted with H2O (3×) and extracted with EtOAc (3×). The combined EtOAc extractions are washed with sat'd NaHCO3 (3×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The crude product is purified by column chromatography (1:1 hexanes:EtOAc, followed by 49:1 EtOAc:triethylamine, followed by 18:1:1 EtOAc:MeOH:triethylamine) to give 4.15 g (40%) of 3,5-dimethyl-1-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine. 1H NMR (CDCl3) 8.62 (d, 2H), 7.30 (d, 2H), 5.48 (s, 2H), 4.07 (m, 2H), 3.03 (m, 2H), 2.51 (m, 2H), 1.12 (d, 6H) ppm. LC-MS (MH+)=306.

Provenance & Evidence