Trimethyl orthoformate → HCID 90303529, compound

Participants

Reaction Steps

A soln. of 5-bromo-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)thiazole (18.80 g, 63.9 mmol) and PPTS (0.80 g, 3.19 mmol) in MeOH (256 mL) was stirred under reflux for 3 h. More PPTS (0.40 g, 1.60 mmol) was added and the mixture was stirred under reflux for additional 2 h. The mixture was conc. in vacuo, the residue was dissolved in MeOH (256 mL) and stirred under reflux for 2 h. The mixture was conc. in vacuo, the residue was dissolved in DCM (256 mL) and treated with trimethyl orthoformate (10.5 mL, 95.8 mmol). The mixture was stirred overnight at RT. Subsequently, additional trimethyl orthoformate (3.5 mL, 31.9 mmol) was added and the mixture was stirred at RT for 1 h. Then, the mixture was conc. in vacuo, the residue was dissolved in DCM (256 mL), treated with AcBr (5.73 mL, 76.7 mmol) and stirred at RT for 90 min. Subsequently, the mixture was conc. in vacuo, the residue was dissolved in MeOH (320 mL) and K2CO3 (17.66 g, 128 mmol) was added to the mixture. After the mixture was stirred at RT for 90 min, the mixture was filtrated and the filtrate was poured into cold aq. sat. NH4Cl. The mixture was extracted with EtOAc, the comb. org. layers were washed with brine, dried over MgSO4, and conc. in vacuo. The residue was purified by means of CC (2-40% EtOAc/Hept) to provide a yellow oil.

Provenance & Evidence