After trying the method, found and tried, by Sunlight and Foxy 2, I decided to try another variant of the procedure. What I wanted was to imitate the conditions in a regular reductive alkylation by hydrogenation. This is how it went...
100 mmol 2-fluorophenylacetone, 1g 5%Pd/C and 120 mmol methylamine in 70ml MeOH[1] was combined in a 250ml round bottomed flask equipped with a reflux condenser and a magnetic stirbar. Glacial acetic acid was added dropwise until pH 6.5 was reached. The mixture was heated to 60 deg C and 400 mmol sodium hypophosphite was added in one portion along with 20ml water. Hydrogen evolution started immediately. The mixture was the allowed to stir for four hours at 60-65 deg C. When the reaction was over diluted HCl was added until pH 2 was reached, then 2 tablespoons celite was added and the catalyst removed by filtration. The solution was distilled under reduced pressure to remove the MeOH. The acidic aqueous solution was extracted twice with 50 ml toluene then basified with NaOH and extracted twice with 50ml toluene. The extracts were combined and dried with MgSO4 and the solvent removed by distillation. This left a amine smelling, slighly yellow oil. The oil was dissolved in 100ml EtOAc and dry HCl in IPA added dropwise until pH 5 was reached. The solution was heated to boiling and concentrated to 50ml. Slow cooling and occacional scratching of the walls induced crystallisation, 100 ml EtOAc was added and the solution was alloved to stand at room temp until crystallisation was complete.
Yield 18.94g 2-fluoro-N-methylamphetamine hydrochloride (93%)
The same procedure gave 2,5-dimethoxy-N-methylampetamine hydrochloride in 89% yield and 2,4-dimethoxy-N-ethylamphetamine in 90% yield.
[1] The solution of methylamine in MeOH was made by dissolving 130 mmol KOH in 55ml MeOH and add a solution of 120 mmol methylamine hydrochloride in 15ml water.
Hypophosphites generates hydrogen in the precense of a catalyst according to: NaH2PO2 + H2O __> NaH2PO3 + H2
Catalytic hydrogenation freak
