[refid]

Would this be a possible way to synthesize Lipitor?

http://bp2.blogger.com/_60ljWjzZHA0/RjE-jhDZJSI/AAAAAAAAAWM/rMjOIr6gD4Q/s1600-h/lip+syn+part1.JPG

http://bp0.blogger.com/_60ljWjzZHA0/RjE9QBDZJRI/AAAAAAAAAWE/SiXV_St_xEc/s1600-h/lip+syn+part+2.JPG

Thanks,
refid

[Yggdrasil]

Lipitor has some chiral centers.  Is your synthesis designed to produce the correct stereoisomer of lipitor?

[refid]

nope just wondering if its the correct route to synthesize the general structure ( i know sterochemistry is very important for drug interaction with the body)

[Congenial]

It is better if you label the structures with numbers,

First, ketone is more active than ester to react with MeMgCl, so the product will react with MeMgCl  quickly upon forming and you will get a tertiary alcohol.

Second, the aldehyde will prefer to condense with itself rather than a cross condensation with the ketone.

Third, pyrrole is electron rich, so nucleophillic substitution is hard to occur on a pyrrole ring without  a strong electron-withdraw group on it (e.g. NO2) . So R2CuLi doesn't work as you expected.

[refid]

First, ketone is more active than ester to react with MeMgCl, so the product will react with MeMgCl  quickly upon forming and you will get a tertiary alcohol.

I used a protecting group to mask the ketone so it only react with the ester

[english]

You might want to use methanol instead.  NaOH will compete for hydrolysis as well as the reaction you want.

Methanol is a bit volatile though.

[Congenial]

I mean your product.  For example the reaction go half,  there are 50% mole of the ester left and  50% mole of the ketone product formed,  what will happen when you add MeMgCl into the mixture? I wish my language can be stronger.

[english]

In the second synthesis your last step (I₂) shows no changes. 

[Congenial]

It's a Iodofom reaction.

[english]

It's a Iodofom reaction.

Right.  Just saw the —OH.  Sneaky bastards.

[refid]

I mean your product.  For example the reaction go half,  there are 50% mole of the ester left and  50% mole of the ketone product formed,  what will happen when you add MeMgCl into the mixture? I wish my language can be stronger.

ahh ic see, would i distill off the ketone and collect and then do the grignard...or what do you suggust?

[kiwi]

I mean your product.  For example the reaction go half,  there are 50% mole of the ester left and  50% mole of the ketone product formed,  what will happen when you add MeMgCl into the mixture? I wish my language can be stronger.

ahh ic see, would i distill off the ketone and collect and then do the grignard...or what do you suggust?

you're missing the point, what happens when you form a ketone in a reaction mixture containing MeMgI? you'll need to upgrade your methodology, say using a weinreb amide instead of an ester as the grignard substrate. but all these reactions seem to be done on the low tech side of things; are you allowed to consider modern methods or is this for an undergrad paper?

[refid]

Im in second year, just finished the introduction to organic chemistry...Im still a newbie at this ... just testing my knowledge of organic chemistry to try synthesize some complex compound  . so about upgrading methodology.. will do im still learning

[kiwi]

Im in second year, just finished the introduction to organic chemistry...Im still a newbie at this ... just testing my knowledge of organic chemistry to try synthesize some complex compound  . so about upgrading methodology.. will do im still learning

good on you, its the best way to learn. but the molecule you've picked is probably a bit beyond the methods they've taught you so far. You could have a play with some other molecules; off the top my head try prozac/fluoxetine. diphenhydramine, or fentanyl. all important molecules, and they should be possible with your background (maybe, i don't know the specifics of your course obviously).

[refid]

I mean your product.  For example the reaction go half,  there are 50% mole of the ester left and  50% mole of the ketone product formed,  what will happen when you add MeMgCl into the mixture? I wish my language can be stronger.

How about this way:


http://img485.imageshack.us/my.php?image=lipsyn1edit2le3.jpg

I think there might be problem with adding acid at certain points

edit HOAc should be Ac2O
edit image