反应详情

温度

100 °C

A solution of 2-methyl-4-thiophen-2-yl-butan-2-ol (630 mg, 3.7 mmol) in 10 ml of THF was treated with LDA (4.6 ml of 2M solution in THF/heptane/ethylbenzene, 9.2 mmol) at −78° C. under nitrogen and the mixture was stirred for 5 minutes. Then, trimethylborate (1 ml, 9.2 mmol) was added in one portion and the cooling bath was removed. After 15 minutes, the mixture was quenched with 50 ml of saturated ammonium chloride solution and extracted twice with EtOAc. The combined organic extracts were washed with brine and evaporated under reduced pressure at room temperature. This crude boronic acid was redissolved in 10 ml of DME and added to a stirred suspension 2,4-dichloro-pyrimidine (275 mg, 1.85 mmol), Pd(PPh3)4 (64 mg, 0.037 mmol), 20 ml of DME and 5 ml of a 10% solution of sodium bicarbonate. This mixture was then kept at reflux (100° C. heat bath) for 90 minutes. After cooling, most of the DME was evaporated and the crude was partitioned between water and EtOAc. The organic layer was separated, washed with 0.2N-HCl, water and brine, dried over sodium sulfate and evaporated. The crude was purified by chromatography on silicagel (EtOAc/hexane:1/1). Yield: 390 mg (77%) of 4-[5-(2-Chloro-pyrimidin-4-yl)-thiophen-2-yl]-2-methyl-butan-2-ol.

1. customthe cooling bath was removed
2. waitAfter 15 minutes
3. customthe mixture was quenched with 50 ml of saturated ammonium chloride solution
4. extractionextracted twice with EtOAc
5. washThe combined organic extracts were washed with brine
6. customevaporated under reduced pressure at room temperature
7. dissolutionThis crude boronic acid was redissolved in 10 ml of DME
8. temperatureat reflux
9. customwas evaporated
10. customthe crude was partitioned between water and EtOAc
11. customThe organic layer was separated
12. washwashed with 0.2N-HCl, water and brine
13. dry with materialdried over sodium sulfate
14. customevaporated
15. customThe crude was purified by chromatography on silicagel (EtOAc/hexane:1/1)