Fmoc-L-beta-homoalanine

193954-23-3

193954-26-6

GENERAL METHOD: Fmoc-Ala-OH (2.00 g, 6.4 mmol) was dissolved in CH2Cl2 and thionyl chloride (7.00 mL, 64.2 mmol) was added. The reaction mixture was refluxed at 55 to 60 °C for 3 h under argon protection and subsequently concentrated under reduced pressure. The residue was dissolved in anhydrous CH2Cl2 and added slowly and dropwise to a solution of (trimethylmethylsilyl)diazomethane (9.63 mL, 19.3 mmol) in CH2Cl2 at 15 to 20 °C under argon protection. After 5 hours of reaction, the reaction was quenched by the addition of dilute acetic acid. The reaction mixture was washed sequentially with brine, 5% Na2CO3 solution and brine, and the organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The intermediate was purified by silica gel fast column chromatography. The purified intermediate was dissolved in a solvent mixture of dioxane and H2O (4:1, v/v), and a catalytic amount of CH3COOAg was added. After stirring at 50 to 80 °C for 2 h, the reaction mixture was filtered, concentrated, dissolved in 5% Na2CO3 solution and extracted with ethyl acetate. The organic layer was washed twice with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by fast column chromatography on silica gel to afford the target product (0.68 g, 33% total yield in two steps).1H NMR (400 MHz, CDCl3): δ = 7.76-7.29 (8H, m), 5.19 (1H, br s), 4.39 (2H, br s), 4.22-4.13 (2H, m), 2.60 (2H, br s ), 1.26 (3H, d, J = 6.0 Hz).