Ammonium Chloride → 1-[1,3]Dioxolan-2-yl-6,6,6-trifluoro-hexan-3-one

Mg (92.0 mmol, 2.2 g) in TBF (80 ml), under an argon atmosphere, was treated with 2-(2-bromoethyl)-[1,3]dioxolane (80 mmol, 9.4 ml), while keeping the internal temperature below 35° C. with the aid of an ice bath. After the addition was complete, the mixture was stirred for 2 h at room temperature, then cooled to −78° C. Crude 4,4,4-trifluoro-N-methoxy-N-methyl butyramide (20 g, prepared above) in THF (40 ml) was cooled to −78° C., then the freshly prepared Grignard reagent was transferred via cannula into the amide solution at −78° C. The resulting mixture was allowed to warm to room temperature, held at room temperature overnight, then poured into saturated aqueous ammonium chloride (200 ml). The mixture was extracted with ethyl acetate (3×75 ml). The combined organics were washed with brine (2×75 ml) and concentrated under reduced pressure to provide crude 1-[1,3]dioxolan-2-yl-6,6,6-trifluoro-hexan-3-one (18 g) 1H NMR (CDCl3) δ4.91 (1H, t, J=4.1), 3.97-3.82 (4H, m), 2.70 (2H, t, J=7.3), 2.57 (2H, t, J=7.2), 2.49-2.34 (2H, m), 2.01 (2H, dt, J=7.3, 4.1).

1. customthe internal temperature below 35° C.
2. additionAfter the addition
3. temperaturecooled to −78° C
4. temperatureto warm to room temperature
5. waitheld at room temperature overnight
6. extractionThe mixture was extracted with ethyl acetate (3×75 ml)
7. washThe combined organics were washed with brine (2×75 ml)
8. concentrationconcentrated under reduced pressure

ORD record

ord-a53311294a5d4cbc8ec0a9f03fddb5c1

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06610730B2