Ethyl bromoacetate → HCID 66654779, compound

Participants

Reaction Conditions

Reaction Steps

A mixture under N2 of (±)-1-(2-allyloxy-4-fluoro-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (200 mg, 0.48 mmol, 1.00 eq.), 1,3-dimethylbarbituric acid (150 mg, 0.96 mmol, 2.00 eq.) and tetrakis(triphenylphosphine) palladium (0) (28 mg, 0.02 mmol, 0.05 eq.) in MeOH (5 mL) was stirred at r.t. for 5 hours. The mixture was partitioned between AcOEt (25 mL) and water (25 mL). The layers were separated and the aq. phase was extracted with AcOEt (2×25 mL). The comb. org. phases were washed with sat. aq. NaCl soln. (1×25 mL), dried over MgSO4, and concentrated in vacuo. To a solution of the residue and Cs2CO3 (468 mg, 1.44 mmol, 3.00 eq.) in DMF (3 mL), ethyl bromoacetate (79 μL, 0.72 mmol, 1.50 eq.) was added. The reaction mixture was stirred at 50° C. for 5 hours. The reaction mixture was diluted with water (25 mL) and AcOEt (50 mL). The layers were separated. The aq. phase was extracted with AcOEt (2×25 mL). The comb. org. phases were washed with water (1×25 mL), sat. aq. NaCl soln. (1×25 mL), dried over MgSO4, and concentrated in vacuo. To a solution of the residue in DMF (2 mL), 1M aq. NaOH (2 mL) was added. The resulting solution was stirred at 50° C. for 5 hours. The solution was neutralized with formic acid (1 mL) and then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the desired acid.

Provenance & Evidence