Rhodium (Chief Bee)
10-11-02 14:50
No 367290
      Indole -> Tryptamine, Grignard-style  Bookmark   

US Pat 2708197


To a grignard reagent prepared from 4.25 grams (0.03 moles) of methyl iodide and 2.0 grams of magnesium in 200ml of ether was added a solution of 5.5g (0.025 moles) of 5-benzyloxyindole in 200ml ether. After heating under reflux for 30 minutes, the mixture was cooled in an ice-bath and to it was added a solution of 3g (0.04 moles) of freshly distilled chloroacetonitrile in 100ml of ether. The mixture was heated vigorously under reflux for 2.5 hours, cooled and hydrolyzed by the addition of a solution of 100 ml 10% aqueous acetic acid. The ether layer was separated and the aqueous layer was extracted with several portions of ether. The ether extracts were combined and washed successively with water, sodium carbonate solution and water, dried over potassium carbonate for at least 24h to give an etheral solution of 5-benzyloxy-3-indoleacetonitrile.


The etheral solution of 5-benzyloxy-3-indoleacetonitrile from above was added dropwise to a solution of 3.7g (0.1 moles) of lithium aluminum hydride in 400ml anhydrous ether, and the solution refluxed for one hour and hydrolyzed by the addition of 500ml ether saturated with water, followed by 50ml 5% NaOH. The etheral layer was decanted and the aqueous alkaline residue was extracted with several 300ml portions of ether. The etheral extracts containing free 5-benzyloxytryptamine were combined and washed with 5% aqueous sodium hydroxide and with water, whereafter the free 5-benzyloxytryptamine was shaken with an equimolar portion of 5% hydrochloric acid. A crystalline precipitate of 5-benzyloxytryptamine hydrochloride separated and was removed by filtration, yield 3.3g (44% from 5-benzyloxyindole). After recrystallization from ethanol-water the mp was 248-250C.