反応 #163420
ord-f3a23f4e3ab04b369e85ffbd7a28a5ab
反応方程式
反応物
反応条件
後処理
- 1workup.STIRRINGthe reaction was stirred for 15 minutes
- 2その他synthesized
- 3workup.STIRRINGthe reaction mixture was stirred overnight at r.t
- 4抽出The reaction mixture was extracted with DCM/H2O
- 5洗浄the organic phase was washed with brine
- 6乾燥dried over sodium sulphate
- 7ろ過filtered
- 8その他evaporated to dryness
- 9その他The residue was purified by gradient flash chromatography (eluent DCM to DCM/methanol 97/3 v/v)
実験手順
1-(3′,4′-Dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid (0.30 g, 0.92 mmol) was dissolved in dry DCM (30 mL); two drops of DMF and oxalyl chloride (78 uL, 0.92 mmol) were added; and the reaction mixture was stirred at r.t. under nitrogen atmosphere for 30 minutes. Additional oxalyl chloride (39 uL, 0.46 mmol) was added and the reaction was stirred for 15 minutes. This solution was added dropwise to a solution of N-(3-acetylamino-2-hydroxypropyl)acetamide (synthesized as reported on J. Org. Chem., 2000, 65(4), 1200, which is incorporated herein by reference in its entirety) and triethylamine (385 uL, 2.76 mmol) in dry DCM (2 mL) and dry DMF (2 mL). 4-Dimethylaminopyridine (34 mg, 0.28 mmol) and dry pyridine (1.5 mL) were added, and the reaction mixture was stirred overnight at r.t. The reaction mixture was extracted with DCM/H2O, and the organic phase was washed with brine, dried over sodium sulphate, filtered and evaporated to dryness. The residue was purified by gradient flash chromatography (eluent DCM to DCM/methanol 97/3 v/v) affording the title compound which was further purified by preparative HPLC to obtain 1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid 2-acetylamino-1-(acetylaminomethyl)ethyl ester (105 mg, 24% yield) as a white solid.