Tryptophan to Tryptamine
Tryptophan (454g) was suspended in tetralin (1150 ml) containing acetone (12.9 g) and the mixture was heated to reflux for 12 hours with vigorous stirring until no more carbon dioxide was evolved and the reaction mixture became clear. The solvent was removed under vacuum, and the residue was distilled under reduced pressure to give a yellow crystalline solid.
Tryptamine to N,N-Dimethyltryptamine (DMT)
Next, 30g of formaldehyde and 120g Tryptamine were disolved in 1800ml of MeOH, to this was slowly added dropwise 50g of NaCNBH3 disolved in 550ml MeOH. Then 14g Glacial Acetic Acid was added dropwise with stirring. The mixture was then stirred for 60 hours. The majority of the MeOH was distilled off (2000 ml collected) to the distillation flask was added 1L of 5% Aq. Ammonia which was extracted with 3x250ml of DCM. The DCM was washed with a salt solution (not saturated but still pretty strong) then the DCM separated and dried with a large portion of anhydrous MgSO4. The DCM was distilled off at atmospheric pressure and then the distillation was continued under vacuum (~1 torr now) until the dimethyltryptamine was collected. Which was recrystalized from boiling hexane with a few mls of Ethyl Acetate added. This afforded 48.8g of DMT, a 35% yield.
Note: The reason for the low yield should be a too low amount of formaldehyde added to the reaction mixture. At least two moles of formaldehyde per mole of tryptamine is needed for complete conversion to DMT.
DMT; Higher yield variation
Tryptamine hydrochloride (10 g, 62.4 mmol) and sodium cyanoborohydride (6.28 g, 100 mmol) in a mixture of methanol (400 mL) and glacial acetic acid (11.76 g, 196 mmol) were cooled to 0°C in an ice bath over a steady stream of nitrogen. A solution of 4.20 g formaldehyde (140 mmol, 11.05 mL of 38% aq. CH2O) in 125 mL of Methanol was added dropwise to the solution over a period of one hour with mild stirring. The flask was stoppered, the reaction allowed to return to room temperature slowly, and allowed to proceed for the next 60 hours. Upon completion the pH was adjusted to 8.0 by the dropwise addition of an aqueous solution of sodium bicarbonate. The mixture was then extracted 4x with 50 mL of ethyl acetate. The combined extracts were washed once with 250mL of brine and dried over MgSO4 (15g) for 15 minutes. The MgSO4 was washed clean with another 75 mL of ethyl acetate. The solvent was reduced to 100 mL on the rotary evaporator. The hot solution was added to a 200mL beaker and covered with plastic wrap which was sealed on with a rubber band. Upon cooling in the freezer overnight, the precipitated DMT was removed by filtration, and dried in the dessicator.
Overall yield: 7.88g, 45 mmol, 67%. The mp is solid, right around 64-67°C.
Removal of N-Methyltryptamine and Tryptamine from DMT
If you're worried about NMT/T contaminating your product just do the workup this way;
Basify the aq. reaction mix to 13-14 with NaOH. Extract repeatedly with DCM. Rotovap off the DCM and add Petroleum Ether, heat to a boil and decant the Pet. Ether from any undissolved material. Cool the Pet. Ether in the freezer and collect any precipitated solids. This will remove any unreacted tryptamine. To remove NMT you can react this mixture with acetic anhydride and seperate. I know that's quite a hassle but it's a good way to cover all the bases as far as purity is concerned.
(Rhodium site archive)
