Propargyl alcohol → 3-(6-Aminopyridin-3-yl)prop-2-yn-1-ol

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Reaction Conditions

Reaction Steps

2-Amino5-bromopyridine (7-1), 10.0 g (57.8 mmol) was stirred in pyrrolidine (96.5 mL, 1.16 mol, 20 equiv) in a flame dried round bottom flask under argon. Propargyl alcohol (10.1 mL, 173 mmol) and tetrakis triphenylphosphine palladium(0) (1.34 g, 1.16 mmol) were added and the solution was degassed 3× by alternating vacuum/Ar. Heat to 80° C. After 18 h the bulk of the pyrrolidine was removed in vacuo and the residue was diluted with water. Extract with CH2Cl2 three times, and the extracts were dried over Na2SO4, filtered and concentrated to provide impure product. The aqueous layer was further extracted ten times with CH2Cl2/nBuOH (95:5). The extracts were dried over Na2SO4, filtered and concentrated. The two samples were combined and were purified in two batches by flash column chromatography (gradient: CH2Cl2 to CH2Cl2/MeOH, 90:10). The product was triurated with ice cold CH2Cl2, filtered, and washed with ice cold CH2Cl2. Afforded the titled compound as a pale yellow solid. 1H NMR (CD3OD) δ 7.96 (d, 1H, J=2.2 Hz), 7.45 (dd, 1H, J=2.4, 8.8 Hz), 6.51 (d, 1H, J=8.8 Hz), 4.36 (s, 2H).

Provenance & Evidence