Ammonium Chloride → (S)-1-(2-fluorophenyl)-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)ethanone

Temperature

-60 °C

A solution of n-butyllithium in hexane (2.50 M; 90 mL) was added dropwise over 25 mins to a solution containing 2-bromofluorobenzene (40.35 g) in THF (250 mL) under a N2 atmosphere at −78° C. The reaction solution was allowed to warm to −60° C. and stir for 60 min. (S)—N-methoxy-N-methyl-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)acetamide (40 g) in THF (25 mL) was added dropwise to the reaction solution, and after stirring at −60° C. for 2 h, aqueous NH4Cl (100 mL) was added to the reaction solution, followed by warming to RT. Brine (200 mL) was added to the reaction solution, and the mixture was extracted with EtOAc (3×400 mL). The combined organic portions were dried over MgSO4, evaporated, and the residue was purified by silica gel column chromatography (1% to 10% EtOAc in hexanes) to obtain the title compound (33.59 g). 1H NMR (400 MHz, CDCl3) δ ppm: 4.40 (pentet, J=6.3 Hz, 1H) 4.81-4.87 (m, 2H), 5.54-5.69 (m, 2H), 5.86 (ddd, J 17.4, 10.4, 7.3 Hz, 1H) 7.12-7.22 (m, 1H) 7.24-7.34 (m, 1H) 7.54-7.63 (m, 1H) 7.94-8.02 (m, 1H).

1. additionwas added dropwise to the reaction solution
2. temperatureby warming to RT
3. extractionthe mixture was extracted with EtOAc (3×400 mL)
4. dry with materialThe combined organic portions were dried over MgSO4
5. customevaporated
6. customthe residue was purified by silica gel column chromatography (1% to 10% EtOAc in hexanes)

ORD record

ord-38a7d078288c4b75bcaf473fb3e6e9b5

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139594B2