反应详情

(S)-5-(Biphenyl-4-yl)-4-[(dimethylphosphonomethyl)-amino]-2-pentenoic acid ethyl ester (536 mg, 1.28 mmol) is dissolved in methanol (1 mL) and treated with 1N sodium hydroxide (2 mL, 2 mmol). The reaction mixture is stirred for 3 hours at room temperature, then 1N hydrochloric acid (5 mL) is added. The carboxylic acid is extracted in methylene chloride (20 mL). The organic layer is separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is suspended in methylene chloride (2 mL) under nitrogen and treated with trimethylsilyl bromide (0.424 mL, 3.21 mmol). The clear solution is stirred at room temperature for 18 hours, then concentrated in vacuo. The residue is triturated with water (5 mL) and the precipitate is filtered off and then dissolved in 1N sodium hydroxide (5 mL). 1N Hydrochloric acid (8 mL) is added to precipitate the product which is filtered and washed with water (10 mL). The solid is suspended in ethanol (5 mL) and stirred for 20 minutes with propylene oxide (2 mL). Concentration in vacuo yields (S)-5-(biphenyl-4-yl)-4-(phosphonomethylamino)-2-pentenoic acid as a white solid; m.p.: 231°-233°.

1. extractionThe carboxylic acid is extracted in methylene chloride (20 mL)
2. customThe organic layer is separated
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. stirringThe clear solution is stirred at room temperature for 18 hours
7. concentrationconcentrated in vacuo
8. customThe residue is triturated with water (5 mL)
9. filtrationthe precipitate is filtered off
10. dissolutiondissolved in 1N sodium hydroxide (5 mL)
11. addition1N Hydrochloric acid (8 mL) is added
12. customto precipitate the product which
13. filtrationis filtered
14. washwashed with water (10 mL)
15. stirringstirred for 20 minutes with propylene oxide (2 mL)
16. concentrationConcentration in vacuo