反应详情

(S)-4-t-Butoxycarbonylamino-5-(biphenyl-4-yl)-pentenoic acid ethyl ester (1.2 g, 3.03 mmol) is stirred for 1 hour in a 1/1 mixture of trifluoroacetic acid and methylene chloride (10 mL). A saturated aqueous solution of sodium bicarbonate (10 mL) is added and the product is extracted in methylene chloride (20 mL). The organic layer is dried over anhydrous sodium sulfate, filtered and cooled to 0° under nitrogen. To that solution is added N,N-diisopropylethylamine (0.633 mL, 3.63 mmol) in methylene chloride (2 mL), followed by a solution of dimethylphosphonomethyl trifiuoromethylsulfonate (Tetrahedron Lett., 1986, 1477; 907 mg, 3.33 mmol) in methylene chloride (2 mL). The mixture is stirred at room temperature for 18 hours. Water (20 mL) and methylene chloride (20 mL) are added. The organic layer is separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel, eluting with ethyl acetate to afford (S)-5-(biphenyl-4-yl)-4-[(dimethylphosphonomethyl)-amino]-2-pentenoic acid ethyl ester as a pale yellow oil (Rf=0.3 in EtOAc).

1. extractionthe product is extracted in methylene chloride (20 mL)
2. dry with materialThe organic layer is dried over anhydrous sodium sulfate
3. filtrationfiltered
4. temperaturecooled to 0° under nitrogen
5. customThe organic layer is separated
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue is purified by flash-chromatography on silica gel
10. washeluting with ethyl acetate