Propane sultone → 3-{[(1S)-1-(benzyloxycarbonyl)-3-methylbutyl]amino}-1-propanesulfonic acid

Participants

Reaction Steps

To a solution of L-Leucine benzylester (2.81 g, 12.7 mmol) in tetrahydrofuran (6 mL), 1,4-dioxane (6 mL) and MeOH (6 mL) was added 1,3-propane sultone (1.40 g, 11.5 mmol). The solution was stirred at reflux for 2.5 hours. The reaction mixture was cooled to room temperature. The solid was filtered and washed with acetone (2×20 mL). The filtrate was evaporated under reduced pressure. The residue was dissolved in acetone (20 mL). The product was precipitated with Et2O (200 mL). The solid material was filtered. Both solids were combined and dissolved in 50% EtOH/water (200 mL). Dowex Marathon C ion exchange resin (strongly acidic) was added to the solution. The suspension was stirred for 15 minutes before the resin was removed by filtration. The filtrate was evaporated under reduced pressure and lyophilized, affording the title compound (1.87 g, 47%). 1H NMR (DMSO, 500 MHz) δ ppm 9.34 (s (broad), 1H), 7.39 (m, 5H), 5.25 (s, 2H), 4.10 (m, 1H), 3.09 (m, 2H), 2.60 (m, 2H), 1.95 (m, 2H), 1.64 (m, 3H), 0.86 (m, 6H). 13C (DMSO, 125 MHz) δ ppm 168.90, 134.91, 128.53, 128.50, 128.41, 67.38, 57.37, 49.17, 45.79, 38.06, 24.07, 22.79, 21.78, 21.33. [α]D=+1.8° (c=0.0017 in water), ES-MS 344 (M+1).

Provenance & Evidence