反应详情

To an ice-cooled solution of 5-(2-fluoro-4-biphenylyl)-4-oxohexanoic acid (500 mg, 1.52 mmoles) in diethyl ether (10 ml) was added dropwise bromine (243 mg, 1.52 mmoles) and the resulting mixture was stirred at room temperature for 3.5 hours. The reaction mixture was concentrated under reduced pressure. A mixture of the afforded residue, N-methylthiourea (164 mg, 1.82 mmoles) and methanol was stirred at 50° C. for 2 hours and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduce pressure. Purification of the residue by medium pressure silica gel column chromatography gave the desired ethyl 2-(4-(1-(2-fluoro-4-biphenylyl)ethyl)-2-methylamino-5-thiazolyl)acetate (209 mg, 0.524 mmole, yield 35%) as a yellow oil.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. stirringwas stirred at 50° C. for 2 hours
3. concentrationconcentrated under reduced pressure
4. customThe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
5. washThe organic layer was washed with water
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated
8. customPurification of the residue by medium pressure silica gel column chromatography