Phenol → HCID 90022830, compound

Participants

Reaction Steps

A mixture under N2 of (±)-4-(2-allyloxy-5-fluoro-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester (261 mg, 0.61 mmol, 1.00 eq.), 1,3-dimethylbarbituric acid (191 mg, 1.21 mmol, 2.00 eq.) and tetrakis(triphenylphosphine) palladium (0) (35 mg, 30 μmol, 0.05 eq.) in MeOH (12 mL) was stirred at r.t. for 18 hours. The mixture was partitioned between AcOEt (55 mL) and water (55 mL). The layers were separated and the aq. phase was extracted with AcOEt (2×55 mL). The comb. org. phases were washed with sat. aq. NaCl soln. (1×55 mL), dried over MgSO4, and concentrated in vacuo. To a solution of the resulting crude phenol and potassium carbonate (252 mg, 1.82 mmol, 3.00 eq.) in DMF (2.1 mL), ethyl bromoacetate (0.1 mL, 0.91 mmol, 1.50 eq.) was added. The mixture was stirred at r.t. for 18 hours. Ethyl bromoacetate (50 μL, 0.46 mmol, 1.33 eq.) was added again and the mixture was stirred at r.t. for 7 hours. LC/MS still showed starting material. Ethyl bromoacetate (67 μL, 0.61 mmol, 1.00 eq.) and potassium carbonate (126 mg, 0.91 mmol, 1.50 eq.) were added again and the mixture was stirred at r.t. for 18 hours. The reaction mixture was diluted with AcOEt and water. The layers were separated and the aq. phase was extracted with AcOEt (2×). The comb. org. extracts were washed with water and sat. aq. NaCl soln., dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flashmaster (column: 50 g, flow: 30 mL/min, 50 fractions of 30 mL, Heptane to Heptane+40% AcOEt) to yield the title compound as an orange oil.

Provenance & Evidence