Hydrochloric Acid → HCID 178455687, compound

To an ice bath cooled solution of ethyl 3-amino-2-fluoro-1-methyl-3-oxopropyl(diethoxymethyl)phosphinate (1.6 g, 5.3 mmol) in THF (15 ml) was added 1 M BH3-THF (12.3 mL, 12.3 mmol) while under an argon atmosphere. After 10 minutes, the solution was heated to reflux for 3 h. The solution was cooled to room temperature and 6 N HCl (100 mL) was added dropwise. The THF was removed by rotovap and another portion of 6 N HCl (100 mL) was added. The mixture was refluxed for 3 h. The solution was cooled, evaporated, co-evaporated with water and then with etanol. The residue was purified ion exchange chromatography (DOWEX® 50WX-8-200, H+ form, 3.5×4.0 cm). The ion exchange resin was prewashed with 2:1 methanol/water. The crude product dissolved in 1:1 methanol/water was loaded onto the column and washed with 1:1 methanol/water. The eluent was changed to 3:1 methanol/concentrated ammonium hydroxide. The appropriate fractions were combined and evaporated to give 150 mg (15%) of a diastereomeric mixture of (3-amino-2-fluoro-1-methylpropyl)phosphinic acid as an oil. Data: 1H NMR (400 MHz, D2O) δ 6.2-7.8 (m, 1H), 4.8-5.2 (m, 1H), 3.2-3.5 (m, 2H), 1.8-2.2 (m, 1H), 1.0-1.2 (m, 3H); MS: m/z=156 (M+H)+.

1. temperaturethe solution was heated
2. temperatureto reflux for 3 h
3. customThe THF was removed by rotovap
4. additionanother portion of 6 N HCl (100 mL) was added
5. temperatureThe mixture was refluxed for 3 h
6. temperatureThe solution was cooled
7. customevaporated
8. customThe residue was purified ion exchange chromatography (DOWEX® 50WX-8-200, H+ form, 3.5×4.0 cm)
9. dissolutionThe crude product dissolved in 1:1 methanol/water
10. washwashed with 1:1 methanol/water
11. customevaporated

ORD record

ord-5ac6acb713984cd0bf08f0bb82cf2fd8

Source dataset

uspto-grants-2005_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06841698B2