3-Methoxyphenethyl alcohol → 2-[2-(3-Methoxyphenyl)ethoxy]-6-(4-piperidinyloxy)pyrazine

Participants

Reaction Steps

A solution of the product obtained in Step 2 above (0.043 g, 0.20 mmol) in DMF (1.1 mL) was added to a mixture of 3-methoxyphenethyl alcohol (0.061 g, 0.40 mmol) and K-t-BuO (1.0 M in tert-butanol; 0.4 mL, 0.40 mmol) in DMF (0.8 mL). The reaction mixture was vortexed for 16 h at 50° C. under nitrogen, quenched with water (0.1 mL) and concentrated in vacuo. The residue was partitioned between water (2 mL) and 4 ethyl acetate (4 mL) and poured through a hydromatrix column, which was eluted with ethyl acetate/Et3N (95:5). Solvents were evaporated off and the residue was dissolved in methanol/water (50 mL) and loaded onto a conditioned weak cation exchange SPE column (1 g, Amberlyst CG-50 I). The column was washed with water (10 mL) and methanol (10 mL). The compound was eluted with aqueous 2.0 M NH3 in methanol (20 m) and concentrated in vacuo. The residue was analysed for identity and purity by LC-UV/MS. Yield: 8 mg (12%). HRMS m/z calcd for C18H23N3O3 (M)+ 329.1739, found 329.1743.

Provenance & Evidence