[crosspost from the other place]
The methods herein described can also probably be applied -- and with better luck -- to the synthesis of another, more popular compound. But I digress. This post discusses the synthesis of alpha-ethyltryptamine from tryptophan. wink
(A bit of terminology: 5-(4H)-oxazolone means that the carbonyl group is at the 5-position and the 4-position is saturated. 5-(2H)-oxazolone means the carbonyl is at the 5 position and the 2 position is saturated. Oxazoles and similar rings are numbered with O as 1 and N as 3.)
Step 1: formation -- reacting an amino acid -- in this case, tryptophan -- with acetic anhydride produces a 5(4H)-oxazolone:
see first attachment
http://its.goofyti.me/u/http://onlinelibrary.wiley.com/doi/10.1002/0471649295.ch7/summary
http://its.goofyti.me/u/http://onlinelibrary.wiley.com/doi/10.1002/bscb.19921010712/abstract
http://its.goofyti.me/u/http://i.imgur.com/N9zhy.gif -- picture of the oxazolone formed from tryptophan.
This is basically the first intermediate in the Erlenmeyer azlactone synthesis, except with an indolethyl attached at 4, and I believe this oxazolone is often [incorrectly] called an azlactone.
The trifluoroacetic version of the oxazolone (as described in the first attachment) can be isomerized by prolonged heating from (4H) to (2H). This isomerization is bad; it makes the molecule useless.
Step 2: The 4-proton is acidic, alkylate with e.g. EtBr/base/PTC (
)
see second attachment
4-alkylation of 5-(4H)-oxazolones, i.e. the thing we're dealing with, has been described. Yay! The review doesn't go into too much detail, though -- it confirms the obvious suspicion that the 4-proton is acidic and forms an enolate, which reacts with electrophiles. They describe some cool enantioselective reactions involving palladium and allenes which constitute way too much effort considering the target compound.
Step 3: Hydrolysis / decarboxylation (NaOH / H2O) yields AET
And we're done, folks!
The methods herein described can also probably be applied -- and with better luck -- to the synthesis of another, more popular compound. But I digress. This post discusses the synthesis of alpha-ethyltryptamine from tryptophan. wink
(A bit of terminology: 5-(4H)-oxazolone means that the carbonyl group is at the 5-position and the 4-position is saturated. 5-(2H)-oxazolone means the carbonyl is at the 5 position and the 2 position is saturated. Oxazoles and similar rings are numbered with O as 1 and N as 3.)
Step 1: formation -- reacting an amino acid -- in this case, tryptophan -- with acetic anhydride produces a 5(4H)-oxazolone:
see first attachment
http://its.goofyti.me/u/http://onlinelibrary.wiley.com/doi/10.1002/0471649295.ch7/summary
http://its.goofyti.me/u/http://onlinelibrary.wiley.com/doi/10.1002/bscb.19921010712/abstract
http://its.goofyti.me/u/http://i.imgur.com/N9zhy.gif -- picture of the oxazolone formed from tryptophan.
This is basically the first intermediate in the Erlenmeyer azlactone synthesis, except with an indolethyl attached at 4, and I believe this oxazolone is often [incorrectly] called an azlactone.
The trifluoroacetic version of the oxazolone (as described in the first attachment) can be isomerized by prolonged heating from (4H) to (2H). This isomerization is bad; it makes the molecule useless.
Step 2: The 4-proton is acidic, alkylate with e.g. EtBr/base/PTC (
)see second attachment
4-alkylation of 5-(4H)-oxazolones, i.e. the thing we're dealing with, has been described. Yay! The review doesn't go into too much detail, though -- it confirms the obvious suspicion that the 4-proton is acidic and forms an enolate, which reacts with electrophiles. They describe some cool enantioselective reactions involving palladium and allenes which constitute way too much effort considering the target compound.
Step 3: Hydrolysis / decarboxylation (NaOH / H2O) yields AET
And we're done, folks!
tryptophantfaaoxazolone.pdf