Trimethyl borate → HCID 57936245, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence