Tetrahydrofuran → 2-Benzyl-4-(tetrahydro-pyran-2-yloxymethyl)-6-p-tolyl-pyrimidine

Participants

Reaction Steps

To a solution of Pd(PPh3)2Cl2 (0.285 g, 0.41 mmol) and CuI in THF (50 mL) (0.148 g, 0.777 mmol) was added Et3N (1.5 mL, 11.0 mmol), p-toluoyl chloride (1.3 mL, 10.0 mmol) and tetrahydro-2-(2-propynyloxy)-2H-pyran (1.4 mL, 10.0 mmol). After stirring for 2.5 h, a solution of 2-phenylacetamidine hydrochloride (2.0 g, 11.7 mmol) in THF/MeOH (1:1, 10 mL) was added followed by additional MeOH (5 mL) and Na2CO3 (3.2 g, 30.0 mmol). The reaction mixture was heated at reflux for 15 h, cooled to rt, diluted with Et2O and filtered through a small pad of diatomaceous earth. The filtrate was concentrated and purified via SiO2 chromatography (10-45% EtOAc/hexanes) to give 2.0 g (53%) of the title compound. 1H NMR (CDCl3): 8.02-8.00 (m, 2H), 7.68 (s, 1H), 7.46-7.44 (m, 2H), 7.30-7.27 (m, 4H), 7.21-7.19 (m, 1H), 4.87 (d, J=14.7, 1H), 4.77 (t, J=3.5, 1H), 4.62 (d, J=15.1, 1H), 4.31 (s, 2H), 3.91-3.86 (m, 1H), 3.57-3.52 (m, 1H), 2.41 (s, 3H), 1.96-1.87 (m, 1H), 1.84-1.72 (m, 2H), 1.66-1.55 (m, 3H).

Provenance & Evidence