2-Fluoro-N-methoxy-N-methylacetamide → 2-Fluoro-1-(pyridin-3-yl)ethan-1-one

Participants

Reaction Steps

N-Methyl-N-methoxyfluoroacetamide (D6) (12.64 g, 0.104 mol) was treated with 3-lithiopyridine as in the method of Description 7 to afford 3-(α-fluoroacetyl)pyridine (9.63 g). This crude material was taken-up in dry methanol (100 ml) and treated with methoxylamine hydrochloride (6.63 g, 0.076 mol) at reflux for 1 h. The reaction mixture was concentrated in vacuo and partitioned between saturated aqueous potassium carbonate (100 ml) and chloroform (3×100 ml). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in ether and insoluble material was removed by filtration. The solvent was removed in vacuo and the residue was distilled to afford the title compound (D9) as an oil (10.22 g, 58%) b.p. 110° C. at 0.5 mmHg (Kugelrohr), which consisted of a 4:1 mixture of Z and E isomers.

Provenance & Evidence