Triethylamine → Methyl 4,4-difluoro-3-oxo-2-(2,6-dimethylmorpholin-4-ylmethylidene)butyrate

Participants

Reaction Conditions

Reaction Steps

Methyl 3-(2,6-dimethylmorpholin-4-yl)acrylate (93.5%, 17.5 g, 82 mmol) and triethylamine (8.8 g, 87 mmol) were initially charged in toluene (150 ml) and cooled to −30° C. At this temperature, difluoroacetyl fluoride (10.0 g, 100 mmol) was introduced. The reaction mixture was stirred at −30° C. for 3 h and then, over a period of 1 hour, warmed to room temperature. The reaction mixture was washed with deionized water (100 ml). After separation of the phases, the aqueous phase was extracted once with toluene (100 ml). The toluene phases were combined and washed with an aqueous saturated NaCl solution (100 ml), and the solvent was then removed under reduced pressure. The residue obtained was 21.4 g of an orange solid which, according to GC analysis, consisted to 90.8% of methyl 4,4-difluoro-3-oxo-2-(2,6-dimethylmorpholin-4-ylmethylidene)butyrate (yield: 85.3%). 1H-NMR (CDCl3): δ=1.2 (s, 3H), 1.25 (s, 3H), 2.95 (m, 1H), 3.25 (m, 1H), 3.5 (m, 1H), 3.75 (m, 2H), 3.8 (s, 3H), 6.6 (t, 1H), 7.85 ppm (s, 1H).

Provenance & Evidence