Tramiprosate → 3-Pivaloylamino-1-propanesulfonic acid

3-amino-1-propanesulfonic acid (2.0 g, 14.4 mmol) was dissolved a NaOH (1.2 g, 30.2 mmol) solution in a mixture of 1,4-dioxane (5 mL) and water (15 mL). The mixture was cooled to 0° C. before pivaloyl chloride (2.8 mL, 21.6 mmol) in 1,4-dioxane (5 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature and it was stirred at 65° C. for 4 h. The solvent was evaporated under reduced pressure. The resulting solid was dissolved in water (30 mL), and treated with Dowex 50WX8 resin. The suspension was stirred for 5 minutes and the resin was removed by filtration. The filtrate was evaporated under reduced pressure. The residual material was suspended in 20% EtOH/Acetone. The mixture was stirres at reflux for 30 seconds. The solid product was collected by filtration, and dried in vacuo, to afford compound DT (1.3 g, 41%). 1H NMR (D2O, 500 MHz) δ ppm 3.16 (t, 2H, J=6.8 Hz), 2.75 (t, 2H, J=7.8 Hz), 1.78 (m, 2H), 1.1 (s, 9H). 13C NMR (D2O, 125 MHz) δ ppm 182.75, 48.70, 38.57, 38.18, 26.65, 24.27. ES-MS 222 (M−1).

1. additionwas added dropwise
2. customThe solvent was evaporated under reduced pressure
3. dissolutionThe resulting solid was dissolved in water (30 mL)
4. additiontreated with Dowex 50WX8 resin
5. stirringThe suspension was stirred for 5 minutes
6. customthe resin was removed by filtration
7. customThe filtrate was evaporated under reduced pressure
8. temperatureat reflux for 30 seconds
9. filtrationThe solid product was collected by filtration
10. customdried in vacuo
11. customto afford compound DT (1.3 g, 41%)

ORD record

ord-cf155817470f46eca12c9d6bb7f3133d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642801B2