3-Butyn-1-OL → HCID 86584412, compound

Participants

Reaction Steps

2,4-Dicloropyrimidine (4.47 g, 0.03M) was dissolved in triethylamine (250 ml) under argon. (Ph3P)2PdCl2 (420 mg, 0.006M, CuI (28 mg, 0.00015M) and 3-butyn-1-ol (2.36 ml, 0.03M) were added and the mixture was stirred at ambient temperature for 18 hrs. After evaporation to dryness, water (250 ml), was added and extracted with dichloromethane. The combined organic phases were dried and evaporated to dryness. The residual oil was chromatographed, eluting with iso-hexane/ethyl acetate 1:1 to yield 4-(2 chloro-4-pyrimidyl)-3-butyn-1-ol as an oil (3.3 g) NMR (CDCl3) d, 8.5, (d, 1H); 7.3, (d, 1H); 3.9, (t, 2H); 2.8, (m, 2H); 1.6, (s, 1H). Mass Spec found MH+ 183. This material was hydrogenated as described above, but in the presence of 1 equivalent of triethylamine, to give the required saturated alcohol which was oxidised using the previously described Swem oxidation to give the required 4-(4-pyrimidyl)-butan-1-al. NMR CDCl3 d, 9.8, (s, 1H); 9.1; (s, 1H); 8.5, (d, 1H); 7.1, (d, 1H); 2.8, (t, 2H); 2.5, (t, 2H); 2.1, (m, 2H). Mass spec found MH− 149. 3-(5-fluoropyrimidin-2-yl)propanal. To a stirred solution of (E)-1-ethoxy-3-(5-fluoropyrimidin-2-yl)prop-2-enyl ethyl ether and (Z)-1-ethoxy-3-(5-fluoropyrimidin-2-yl)prop-2-enyl ethyl ether (9.7 g, 43 mmol) in dry ethanol (100 ml) at room temperature under an atmosphere of argon, was added 10% palladium on activated charcoal (1.0 g). The reaction flask was then evacuated and filled with hydrogen gas. The mixture was then stirred for 18 hours at room temperature. The reaction was then filtered through a pad of celite and evaporated under reduced pressure to give a yellow oil (8.7 g, 89%). To a solution of this oil (15 g, 66 mmol) in THF (200 ml) at room temperature was added an aqueous solution of hydrochloric acid (36 ml of a 2M solution, 72 mmol) and the reaction was stirred at room temperature for 3 hours. The reaction was then diluted with ethyl acetate (100 ml) and the pH of the mixture brought to pH=9 by the addition of aqueous sodium hydrogen carbonate solution (saturated, 100 ml). The layers were then separated and the aqueous phase extracted with ethyl acetate (3×100 ml). The combined organic extracts were then dried (Na2SO4), filtered and evaporated under reduced pressure to give 3-(5-fluoropyrimidin-2-yl)propanal (16 g) which was used without further purification. 1H NMR (CDCl3): 9.90 (s, 1 H), 8.50 (s, 2 H), 3.33 (dd, 2 H, J=6.9, 6.9 Hz), 3.00 (dd, 2 H, J=6.9, 6.9 Hz).

Provenance & Evidence