Methanol → HCID 19003549, compound

Participants

Reaction Steps

Sodium (2.53 g, 110 mmol) was dissolved in methanol (250 mL) and (Methoxymethyl)triphenylphosphonium chloride (37.71 g. 110 mmol) was added. After 5 min 2-Fluorobenzaldehyde (10.54 g, 100 mmol) was added and the mixture was allowed to stir for 16 h at reflux. After cooling, the reaction was filtered and concentrated in vacuo, the residue was triturated with hexane and refiltered. After removal of the solvent in vacuo, the residue was dissolved in 110 mL of methanol and treated with N-Bromosuccinimide (18.07 g, 100 mmol). After 20 min at room temperature, the solvent was removed in vacuo and the residue was filtered through silica gel with ether as the eluent to afford α-Bromo-2-fluorophenylacetaldehyde dimethyl acetal as a colorless oil. This material was dissolved in DMF (50 mL) and treated with sodium azide (2.71 g, 42 mmol) and sodium iodide (312 mg, 2.1 mmol) and heated at 120° C. for 18 h. The reaction mixture was diluted with water and the producted was extracted with ether to afford the corresponding azide after removal of solvent. This material was dissolved in methanol (125 mL) and hydrogenated at 50 psi over Lindlar catalyst (2 g) for 20 h. After filtration, the solvent was removed in vacuo to afford α-Amino-2-fluorophenylacetaldehyde dimethyl acetal as a colorless oil.

Provenance & Evidence