反应详情

6-Chloro-8-(3-fluorophenyl)-2-iodo-9-methyl-9H-purine (1076 g) was dissolved in 10 liters of tetrahydrofuran and 97.2 g of bistriphenylphosphine palladium dichloride, 26.4 g of cuprous iodide and 248 g of 1-ethynylcyclopentanol were added thereto. Into this mixture were added dropwise 331 ml of triethylamine within 15 minutes keeping the bulk temperature at not higher than 26° C. in a nitrogen atmosphere. After reacting at room temperature for 4 hours, the reaction solution was diluted with 10 liters of ethyl acetate and washed with 4 liters of a saturated ammonium chloride solution and 1 liter of brine. The organic layer was dried over 2 kg of anhydrous sodium sulfate and filtered followed by concentrating to an extent of 3 liters. The resulting residue was diluted with 4 liters of hexane-ethyl acetate (1:1), filtered and washed with 1 liter of hexane to give 732 g of 1-{2-[6-chloro-8-(3-fluorophenyl)-9-methyl-9H-2-purinyl]-1-ethynyl}-1-cyclopentanol. The yield was 88%.

1. customhigher than 26° C.
2. washwashed with 4 liters of a saturated ammonium chloride solution and 1 liter of brine
3. dry with materialThe organic layer was dried over 2 kg of anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationby concentrating to an extent of 3 liters
6. additionThe resulting residue was diluted with 4 liters of hexane-ethyl acetate (1:1)
7. filtrationfiltered
8. washwashed with 1 liter of hexane