18% |
Stage #1: 4-chloro-6-phenylpyrimidine; (2-(tert-butyl)phenyl)boronic acid With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tris(2,6-dimethoxyphenyl)phosphine In water; toluene at 100℃; for 24h; Inert atmosphere;
Stage #2: With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate In water; toluene at 100℃; for 23h; Inert atmosphere; |
2.1 Synthesis of 4-(2-tert-butylphenyl)-6-phenylpyrimidine (abbreviation: Hppm-tBup)
First, 1.0 g of 4-chloro-6-phenylpyrimidine, 1.1 g of 2-tert-butylphenylboronic acid, 4.0 g of potassium phosphate, 39 mL of toluene, and 3.9 mL of water were put in athree-neck flask equipped with a reflux pipe, and the air in the flask was replaced with nitrogen. In this container were added 48 mg of bis(dibenzylideneacetone)palladium(0), namely Pd2(dba)3, and 190 mg of tris(2,6-dimethoxyphenyl)phosphine, and heating was performed at 100 °C for 7 hours.Then, 24 mg of Pd2(dba)3 and 46 mg of tris(2,6-dimethoxyphenyl)phosphine were added and heating was performed at 100 °C for 17 hours. After that, 12 mg of palladium acetate and 44 mg of 2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl (abbreviation: S-Phos) were added and heating was performed at 100 °C for 15 hours.. Furthermore, 5.9 mg of palladium acetate and 27 mg of S-Phos (abbreviation) were added and heating was performed at 100 °C for 8 hours. Then, 0.10 g of 2-tert-butylphenylboronic acid, 2.0 g of potassium phosphate, 13 mg of palladium acetate, and 12 mg of S-Phos (abbreviation) were added and heating was performed at 100 °C for 21 hours. An organic layer was extracted from the obtained mixture withthe use of ethyl acetate and was washed with saturated brine. Magnesium sulfate was added and the mixture was subjected to filtration. The solvent in the filtrate was distilled off to give a residue. The residue was purified by neutral silica gel column chromatography using a mixed solvent of ethyl acetate and hexane in a ratio of 1:4 as a developing solvent, so that 0.27 g of Hppm-tBup (abbreviation) that is an objectivesubstance was obtained as a yellowish white soHd in a yield of 18 %. A synthesis scheme of Step 1 is shown in (b-1) below. |