Dichloromethane → HCID 68775088, compound

To a stirred solution of (E)-tert-butyl 4-(3,4-difluorophenoxy)-3-fluorobut-2-enylcarbamate (0.061 g, 0.19 mmol [synthesized from (E)-tert-butyl 3-fluoro-4-hydroxybut-2-enylcarbamate and 3,4-difluorophenol following procedure F]) in CH2Cl2 (4.5 mL) at room temperature was added trifluoroacetic acid (0.5 mL). The reaction mixture was allowed to stir for 2 h until no further starting material remained by thin layer chromatography analysis. The solvent was then removed under reduced pressure and the residue taken up in diethyl ether (20 mL) and water (30 mL), and the pH adjusted to ˜pH 1 by addition of 0.1 M HCl (aq.). The aqueous layer was extracted with a further portion of diethyl ether (10 mL) before addition of 2 M NaOH solution to bring the pH up to ˜pH 12. The alkaline layer was extracted with diethyl ether (2×20 mL) and the organics combined and washed with brine (10 mL), dried over MgSO4, filtered and solvent removed under reduced pressure to afford the amine as a clear oil (0.061 g). This product was dissolved in diethyl ether and treated dropwise with HCl (2 M solution in diethyl ether; 0.4 mL) which resulted in the formation of a colorless precipitate. After standing for 20 minutes the precipitate was filtered, washed with diethyl ether (2×2 mL) and dried under vacuum to yield (E)-4-(3,4-difluorophenoxy)-3-fluorobut-2-en-1-amine hydrochloride (0.030 g, 62%) as a fine colorless powder; m.p.=139-140° C.; 1H-NMR (200 MHz, CD3OD): δppm: 3.70 (2H, d, J 7.4 Hz), 4.76 (2H, d, J 18.2 Hz), 5.54 (1H, dt, J 18.1, 8.3 Hz), 6.74-6.83 (1H, m), 6.90-7.01 (1H, m), 7.20 (1H, q, J 19.2).

1. customThe solvent was then removed under reduced pressure
2. additionby addition of 0.1 M HCl (aq.)
3. extractionThe aqueous layer was extracted with a further portion of diethyl ether (10 mL) before addition of 2 M NaOH solution
4. extractionThe alkaline layer was extracted with diethyl ether (2×20 mL)
5. washwashed with brine (10 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customsolvent removed under reduced pressure

ORD record

ord-648f983bd94946758f8703322ee1176e

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426587B2