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I have never split isomers. Can anyone who has done this process clear this up for me.
There is L+ tartaric acid {which is the dexto isomer, what is easy to buy )
And D-tartaric acid(which is Levo, what is hard to buy besides from china)
I am a little bit confused reading threads and articles about actually doing it. So say i use L+ tartaric acid which is dextro isomer, and i have 1 mole of freebase meth/ampt. Am i using this to crystallize the full mole of freebase to then produce
D meth/ampht D tartate and L meth/ampht D tartate, which in turn will give these two isomer different solubilities?
Or will the L+ tartar acid selectivity crystallize the D isomer of my freebase, which then this will mean i need 0.5mole of L+tartaric acid for 1Mole of freebase.
I have read alot of conflicting infomation, its very confusing when it comes to tartaric acid. If anyone has experience, it will be well appreciated.
I divided 70gr of racemic freebase(not steam distilled and no acid-base washing made just extracted and dried from the NaBH4 P2P reduction) in 2 equal parts of 35gr each. With the first 35 gr I did video process but with some different reagents and with the other 35gr I did the method that I use to make that is similar to the video process:
- Method 1(Video method)
- 35gr pure freebase
- 42gr L-tartaric
- 205ml Methanol
The amounts are like video ratio but methanol I decided to use a 12% less due ethanol in video is a 88% solution.
I added the acid to the flask later the methanol and finally the freebase.
Once I started stirring immediately happened what usually happened to me in the rest of the processes I have tried for this purpose the solid salts precipitated quickly forming a mass.
I reflux it during one hour, with heating the mass come a thick liquid.
After the refluxing hour I keep it at RT around 4-5 hours until no new solids are visible created in the mixture.
I filtered it and keep in different pots the solid and the liquid part.
-Liquid part
I get cold the liquid part in the freezer with a NaOH solution to avoid excess heat in the alkalinization step.
I added slowly the NaOH solution to the mixture until ph13 and add it to a separation funnel during 30 min.
I take out the aqueous bottom layer and keep it , the thin oil top layer is kept in a pot.
I extract with DCM the aqueous layer and add these DCM extractions to oil layer.
I dried it with anhydrous sodium sulfate and filtered it.
I evaporated the DCM and 10gr of D-meth freebase obtained(don't looks as clean as it should)
- Solid part
I added more or less the same ml of warm water than gr of the solids weight, they has been dissolved it with stirring and let it cool down.
I added slowly the cold NaOH solution until ph13 and add it to a separation funnel during 30 min.
The next steps are exactly the same as the liquid part process.
After DCM is evaporated I got 15gr of L-meth freebase quite "dirty" too
- Method 2(the one I usually do and similar to the video method)
- 35gr pure freebase
- 41,2gr L-tartaric
- 412ml Methanol
Methanol and tartaric are mixed until complete dissolution, freebase is added while stirring and continue stirring vigorously 2-3min.
Let it at RT during 24 hours until the complete solid mass is formed(if in a couple of hours no solids are formed you should stir it again)
It's filtered and now are exactly the same steps as the other method.
- In the liquid part once I had all the DCM extractions I decided to make an acid-base washing, even the DCM color looks cleaner than the other one, to avoid to be "dirty" like the first method happened and I obtained 10gr of D-meth absolutely clean and pure(pic link at the bottom)
- In the solid part 13gr of enough clean L-meth freebase without acid-base washing obtained.
- Cleaning issue could be fixed during the crystallization stage too are many ways.
Obviously is very difficult to check how much D or L are in reality in the stuff only with Chiral analysis not easy accessible.
I also know that it is not the most correct to compare two methods using some different reagents but in reality they do practically the same function in the process.
In short, similar methods and yields the main differences are that in the second one you can avoid the reflux(so could be easier) and the final freebases looks cleaner than the others method.
When I will have free time again like this weekend(unfortunately not usual :-( only will be remaining to test in small scale the"mexican"method for meth isomer separation is quite different and I only did it in big scale although I finally decided to use the method explained for big scale too.
These would be the 3 methods that I did and I can talk about them with experience.
About when and how to make an acid-base washing instead steam distillation...etc etc needs a complete and long post the same for crystallization.
I'm thinking to post all the possible and more profitable options during the route from BMK(5449) to D-Meth HCL but this would be a long work and I don't know when I will have enough time again hahah at least is planned.
Thanks.
↑View previous replies…
btcboss2022This is the way how isomer separation looks like after 1 hour with method 2 ;-)
btcboss2022Hello btcboss2022 I tested their method, unfortunately it didn't work for me. Everything worked out wonderfully with the precipitation. Unfortunately, with the separation of the freebase from methanol I did you something wrong, could you explain the separation of the liquid phase again in how far you separate it?
Acab1312Is not my method hahah but ok I understood you, what you did exactly and what happened?
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Ok I have the results of my tests trying to follow the video method but the similar reagents that I have on hand and that I usually use.
I divided 70gr of racemic freebase(not steam distilled and no acid-base washing made just extracted and dried from the NaBH4 P2P reduction) in 2 equal parts of 35gr each. With the first 35 gr I did video process but with some different reagents and with the other 35gr I did the method that I use to make that is similar to the video process:
- Method 1(Video method)
- 35gr pure freebase
- 42gr L-tartaric
- 205ml Methanol
The amounts are like video ratio but methanol I decided to use a 12% less due ethanol in video is a 88% solution.
I added the acid to the flask later the methanol and finally the freebase.
Once I started stirring immediately happened what usually happened to me in the rest of the processes I have tried for this purpose the solid salts precipitated quickly forming a mass.
I reflux it during one hour, with heating the mass come a thick liquid.
After the refluxing hour I keep it at RT around 4-5 hours until no new solids are visible created in the mixture.
I filtered it and keep in different pots the solid and the liquid part.
-Liquid part
I get cold the liquid part in the freezer with a NaOH solution to avoid excess heat in the alkalinization step.
I added slowly the NaOH solution to the mixture until ph13 and add it to a separation funnel during 30 min.
I take out the aqueous bottom layer and keep it , the thin oil top layer is kept in a pot.
I extract with DCM the aqueous layer and add these DCM extractions to oil layer.
I dried it with anhydrous sodium sulfate and filtered it.
I evaporated the DCM and 10gr of D-meth freebase obtained(don't looks as clean as it should)
- Solid part
I added more or less the same ml of warm water than gr of the solids weight, they has been dissolved it with stirring and let it cool down.
I added slowly the cold NaOH solution until ph13 and add it to a separation funnel during 30 min.
The next steps are exactly the same as the liquid part process.
After DCM is evaporated I got 15gr of L-meth freebase quite "dirty" too
- Method 2(the one I usually do and similar to the video method)
- 35gr pure freebase
- 41,2gr L-tartaric
- 412ml Methanol
Methanol and tartaric are mixed until complete dissolution, freebase is added while stirring and continue stirring vigorously 2-3min.
Let it at RT during 24 hours until the complete solid mass is formed(if in a couple of hours no solids are formed you should stir it again)
It's filtered and now are exactly the same steps as the other method.
- In the liquid part once I had all the DCM extractions I decided to make an acid-base washing, even the DCM color looks cleaner than the other one, to avoid to be "dirty" like the first method happened and I obtained 10gr of D-meth absolutely clean and pure(pic link at the bottom)
- In the solid part 13gr of enough clean L-meth freebase without acid-base washing obtained.
- Cleaning issue could be fixed during the crystallization stage too are many ways.
Obviously is very difficult to check how much D or L are in reality in the stuff only with Chiral analysis not easy accessible.
I also know that it is not the most correct to compare two methods using some different reagents but in reality they do practically the same function in the process.
In short, similar methods and yields the main differences are that in the second one you can avoid the reflux(so could be easier) and the final freebases looks cleaner than the others method.
When I will have free time again like this weekend(unfortunately not usual :-( only will be remaining to test in small scale the"mexican"method for meth isomer separation is quite different and I only did it in big scale although I finally decided to use the method explained for big scale too.
These would be the 3 methods that I did and I can talk about them with experience.
About when and how to make an acid-base washing instead steam distillation...etc etc needs a complete and long post the same for crystallization.
I'm thinking to post all the possible and more profitable options during the route from BMK(5449) to D-Meth HCL but this would be a long work and I don't know when I will have enough time again hahah at least is planned.
Thanks.
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- By Acab1312
This is the way how isomer separation looks like after 1 hour with method 2 ;-)
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Hello btcboss2022 I tested their method, unfortunately it didn't work for me. Everything worked out wonderfully with the precipitation. Unfortunately, with the separation of the freebase from methanol I did you something wrong, could you explain the separation of the liquid phase again in how far you separate it?