Ethanamine, 2-fluoro-, hydrochloride → HCID 178506036, Verbindung

Temperatur

0 °C

2-Fluoroethylamine hydrochloride salt (282.4 mg, 2.83 mmol) was suspended in 1:1 THF:DCM (6 mL) followed by addition of DIPEA (2.5 mL, 14.35 mmol). The mixture was cooled to 0° C. followed by slow addition of thiophosgene (217 uL, 2.8 mmol) by syringe over five minutes then allowed to slowly warm to room temperature over 30 minutes. 4-Bromobenzene-1,2-diamine (530 mg, 2.8 mmol) was then added and the reaction mixture was allowed to stir at room temperature over an additional 12 h. The mixture was concentrated and the residue partitioned with ethyl acetate and 10% aqueous citric acid. The organic phase was washed twice with additional 10% aqueous citric acid then brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude mixture of thiourea thus obtained was taken into THF (15 mL) followed by addition of mercury (II) oxide (640 mg, 2.95 mmol). The mixture was brought to reflux for 6 h then stirred an additional 60 h at room temperature. The crude mixture was filtered through a bed of celite with ethyl acetate washing and the filtrate concentrated then taken back into ethyl acetate. The organic solution was washed once with 1 M aqueous hydrochloric acid and the organic phase discarded. The aqueous phase was filtered to remove trace insoluble residue and the filtrate basified to pH 9-10 by dropwise addition of 50% aqueous sodium hydroxide. The aqueous phase was then extracted once with ethyl acetate and the organic solution was washed with brine then dried over anhydrous sodium sulfate, filtered and concentrated to afford crude 5-bromo-N-(2-fluoroethyl)-1H-benzo[d]imidazol-2-amine (390 mg, 53% yield) which was carried forward without further purification. MS (EI) for C9H9BrFN3: 258, 260 (MH+).

1. temperatureto slowly warm to room temperature over 30 minutes
2. concentrationThe mixture was concentrated
3. customthe residue partitioned with ethyl acetate and 10% aqueous citric acid
4. washThe organic phase was washed twice with additional 10% aqueous citric acid
5. dry with materialbrine, dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. additionThe crude mixture of thiourea
9. customthus obtained
10. temperatureto reflux for 6 h
11. stirringthen stirred an additional 60 h at room temperature
12. filtrationThe crude mixture was filtered through a bed of celite with ethyl acetate washing
13. concentrationthe filtrate concentrated
14. washThe organic solution was washed once with 1 M aqueous hydrochloric acid
15. filtrationThe aqueous phase was filtered
16. customto remove trace insoluble residue
17. additionthe filtrate basified to pH 9-10 by dropwise addition of 50% aqueous sodium hydroxide
18. extractionThe aqueous phase was then extracted once with ethyl acetate
19. washthe organic solution was washed with brine
20. dry with materialthen dried over anhydrous sodium sulfate
21. filtrationfiltered
22. concentrationconcentrated

ORD-Eintrag

ord-ea472b75e7624919ba3f64ab62f93393

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08648066B2