Hydrochloric Acid → HCID 11041808, compound

Temperature

23 °C

Boc-D-3,4-Difluorophenylalanine (3.05 g, 11.0 mmol, 1 equiv) was dissolved in 1,4-dioxane (10 mL), and a solution of HCl in 1,4-dioxane (4.0 M, 10 mL) was added. The reaction was stirred at 23° C. for 5 h, then the solvent was removed under reduced pressure. The residue was dissolved in 1 M H2SO4 (22 mL), cooled to 0° C. and 2 N NaNO2 (22 mL) was added via addition funnel under argon. The reaction mixture was stirred at 0° C. for 3 h and warmed to room temperature overnight. The resulting mixture was extracted with MTBE (3×40 mL), dried over Na2SO4 and concentrated. The residue was recrystallized from ether/petroleum ether to afford the title intermediate (1.29 g, 58%) as off-white solid. 1H NMR (DMSO-d6) δ 0.82-0.86 (m, 2H), 1.10-1.27 (m, 4H), 1.40-1.48 (m, 2H), 1.63-1.78 (m, 5H), 3.95-4.00 (m, 1H).

1. customthe solvent was removed under reduced pressure
2. dissolutionThe residue was dissolved in 1 M H2SO4 (22 mL)
3. temperaturecooled to 0° C.
4. addition2 N NaNO2 (22 mL) was added via addition funnel under argon
5. stirringThe reaction mixture was stirred at 0° C. for 3 h
6. temperaturewarmed to room temperature overnight
7. extractionThe resulting mixture was extracted with MTBE (3×40 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customThe residue was recrystallized from ether/petroleum ether

ORD record

ord-72f72ecb3ee647709c393daee85e8970

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06514997B2