(S)-2-Amino-3-(6-fluoro-1H-indol-3-yl)-propionic acid → HCID 67186837, compound

Temperature

0 °C

6-Fluorotryptophan (1.9 g, 9.153 mmol) was dissolved in THF (50 mL) and cooled to 0° C. in an ice bath. BH3.Me2S complex (2.55 mL, 26.87 mmol) was added and the reaction mixture was heated at reflux for 21 h. The reaction mixture was then cooled in an ice bath and cautiously quenched by the dropwise addition of MeOH (5 mL). The crude reaction mixture was then concentrated in vacuo. The crude product was dissolved in EtOAc (50 mL) and extracted with aqueous NaOH (20% w/v, 2×50 mL) after which the combined aqueous fractions were extracted with EtOAc (2×50 mL), and the combined organic fractions were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (2.24 g, quantitative) as a white semi-solid that was used without further purification. δH (CD3OD) 7.28 (1H, dd, J 8.9 and J 5.5 Hz), 6.85 (1H, s), 6.83 (1H, dd, J 10.0 and J 2.3 Hz), 6.57 (1H, dt, J 8.1 and J 8.6 Hz), 3.37 (1H, dd, J 10.7 and J 4.3 Hz), 3.19 (1H, dd, J 10.7 and J 6.8 Hz), 2.92 (1H, m), 2.67 (1H, dd, J 14.1 and J 5.8 Hz), 2.47 (1H, dd, J 14.3 and J 7.5 Hz). No exchangeable protons were observed. LCMS (ES+) 208.0 (M)+, RT 1.30 minutes (Method 1).

1. additionMe2S complex (2.55 mL, 26.87 mmol) was added
2. temperaturethe reaction mixture was heated
3. temperatureat reflux for 21 h
4. temperatureThe reaction mixture was then cooled in an ice bath
5. customcautiously quenched by the dropwise addition of MeOH (5 mL)
6. customThe crude reaction mixture
7. concentrationwas then concentrated in vacuo
8. dissolutionThe crude product was dissolved in EtOAc (50 mL)
9. extractionextracted with aqueous NaOH (20% w/v, 2×50 mL) after which the combined aqueous fractions
10. extractionwere extracted with EtOAc (2×50 mL)
11. washthe combined organic fractions were washed with brine (50 mL)
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-f3e6f039b3e042bf95ac1867117d846d

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242116B2