Hydrogen Bromide → Metyrosine

Temperatur

120 °C

To a 100 mL flask with a reflux condenser was charged amide 4 (5.50 g of a mixture containing 4 (3.37 g, 16.1 mmol) and phenylacetamide (2.13 g)) and 48% HBr (30 mL). The solution was heated for 5 h at 120° C. and was cooled to room temperature. H2O (60 mL) was added and the solution was washed with EtOAc (3×35 mL). The aqueous phase was concentrated in vacuo to provide a beige paste. The paste was dissolved in H2O (15 mL) and the resulting mixture was heated to 65° C. Activated carbon (300 mg, Type NORIT SX) was added and the mixture was stirred for 15 min, was filtered and the filter pad was washed with water (2×4 mL). The combined filtrates were heated to 55° C. and the pH was adjusted to 5-6 using 32% aq. NH3. The mixture was cooled to 0° C., was stirred for 15 min and was filtered. The collected solids were washed with cold water (2×5 mL) and were dried in vacuo to provide (−)-α-methyl-L-tyrosine (or metyrosine) 1 (2.65 g, 84%) as a white solid. HPLC (Zorbax C18, NaH2PO4 10 mM pH=3/MeCN (100:0) 10 min, (100:0) to (0:100) 15 min, 0:100 5 min) tR=10.1 min. Chiral HPLC (Nucleosil Chiral-1, CuSO4 10 mM/MeCN 10:1) tR=16.9 min. m.p.=320-321° C. [α]546=+201° (c=0.5 Copper complex solution) (lit.2+185-190° Copper complex solution preparation: Solution A (anhydrous NaOAc dissolved in H2O (150 mL) in 250 mL volumetric flask, glacial acetic acid (50 mL) added and diluted to volume with H2O) mixed with Solution B (cupric sulfate (62.5 g) diluted to volume with H2O in a 200 mL volumetric flask) in a 1 L volumetric flask and was diluted to volume with H2O. Metyrosine solution (5 mg/mL) was prepared in this solution.

1. additionTo a 100 mL flask with a reflux condenser was charged
2. temperaturewas cooled to room temperature
3. washthe solution was washed with EtOAc (3×35 mL)
4. concentrationThe aqueous phase was concentrated in vacuo
5. customto provide a beige paste
6. temperaturethe resulting mixture was heated to 65° C
7. additionActivated carbon (300 mg, Type NORIT SX) was added
8. filtrationwas filtered
9. washthe filter pad was washed with water (2×4 mL)
10. temperatureThe combined filtrates were heated to 55° C.
11. temperatureThe mixture was cooled to 0° C.
12. stirringwas stirred for 15 min
13. filtrationwas filtered
14. washThe collected solids were washed with cold water (2×5 mL)
15. customwere dried in vacuo

ORD-Eintrag

ord-812de80ff0734b2caea561d80383a366

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08841486B2