反应详情

温度

0 °C

Bis(trimethylsilyl)phosphonite was generated as described in WO 01/042252 using N,O-bis-(trimethylsilyl)acetamide (3.0 mL; 12.1 mmol) and ammonium hypophosphite (1.0 g; 12.0 mmol). The resulting reaction mixture was cooled to 0° C. and a solution of ethyl 2-({6-[(tert-butoxycarbonyl)amino]pyridin-3-yl}methyl)acrylate (0.72 g; 2.35 mmol), in methylene chloride (4 mL) was added dropwise. The reaction was stirred overnight at room temperature. Methanol was added at 0° C. followed by water. The reaction mixture was concentrated. The remaining residue was dissolved in water and purified by preparative HPLC (0.1 M NH4Ac (aq)/CH3CN, 1/0→0/1), concentrated and lyophilized to afford 0.56 g (64%) of 2-({6-[(tert-butoxycarbonyl)amino]pyridin-3-yl}methyl)-3-ethoxy-3-oxopropylphosphinic acid.

1. customThe resulting reaction mixture
2. concentrationThe reaction mixture was concentrated
3. dissolutionThe remaining residue was dissolved in water
4. custompurified by preparative HPLC (0.1 M NH4Ac (aq)/CH3CN, 1/0→0/1)
5. concentrationconcentrated