Facile preparation of N-methyl secondary amines by titanium(IV)isopropoxide-mediated reductive amination of carbonyl compounds
JCS Perkin Trans 1, 2527-31 (1998)
A simple, mild and efficient procedure for obtaining N-methyl secondary amines from aldehydes and ketones is reported. Treatment of carbonyl compounds with methylamine hydrochloride, triethylamine and titanium(IV) isopropoxide, followed by in situ sodium borohydride reduction and straightforward aqueous work-up, affords clean products in good to excellent yields.
Reductive amination of MDP2P with MeNH2.HCl, Ti(iPrO)4, NaBH4 and Et3N
A mixture of 3,4-Methylenedioxyphenyl-2-propanone (1.78g, 10 mmol), titanium(IV)isopropoxide (5.9ml, 20 mmol), methylamine hydrochloride (1.35 g, 20 mmol) and triethylamine (2.79ml, 20 mmol) in 15ml absolute ethanol (or methanol) was stirred (preferably under inert atmosphere) room temp for 8–10 h. Sodium borohydride (0.57g, 15 mmol) was then added and the resulting mixture was stirred for an additional 7–8 h at ambient temperature. The reaction was then quenched by pouring into 30ml 2M aqueous ammonia, the resulting inorganic precipitate was filtered off, and washed with 50ml dichloromethane. The organic layer was separated and the remaining aqueous layer was extracted once with 50ml dichloromethane. The combined organic extracts were next extracted once with hydrochloric acid (1 M, 25ml) to separate the neutral materials. The acidic aqueous extracts were washed once with 50ml dichloromethane, then treated with dilute aqueous sodium hydroxide to pH 10–12, and extracted with 3x50ml dichloromethane. The combined organic extracts were washed with 50ml brine, dried over MgSO4 and concentrated in vacuo to afford N-Methyl-3,4-Methylenedioxyphenyl-2-aminopropane in good yield.
