Boron trifluoride etherate → Tert-butyl 5,5,5-trifluoropentanoate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 5,5,5-trifluoropentanoic acid (5 g, 32.0 mmol) in THF (30 mL) and hexane (30 mL) at 0° C., was added tert-butyl 2,2,2-trichloroacetimidate (11.46 mL, 64.1 mmol). The mixture was stirred for 15 min at 0° C. Boron trifluoride etherate (0.406 mL, 3.20 mmol) was added and the reaction mixture was allowed to warm to room temperature overnight. To the clear reaction mixture was added solid NaHCO3 (5 g) and it was stirred for 30 min. The mixture was then filtered through MgSO4 and washed with hexanes (200 mL). The solution was allowed to rest for 45 min, and the resulting solid material was removed by filtering through the same MgSO4 filter again, The filter cake was washed with hexanes (100 mL) and the filtrate was concentrated under reduced pressure without heat. The volume was reduced to about 30 mL, and the mixture was filtered through a clean fritted funnel, washed with hexane (5 mL), and then concentrated under reduced pressure without heat. The resulting neat oil was filtered through a 0.45 μm nylon membrane filter disk to provide Preparation A-1A (6.6 g, 31.4 mmol 98% yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ ppm 1.38 (s, 9H) 1.74-1.83 (m, 2H) 2.00-2.13 (m, 2H) 2.24 (t, J=7.28 Hz, 2H).

Provenance & Evidence