D-LAME To LA?
- Thread starter Blammo
- Start date
I will paste here a conversation I've had about this exact topic with a professional chemist:
Them: Hi, sorry to get back to you so late.
I asked my friend but he didn't inform me, maybe for commercial reasons, I guess you can use a methanol solution of KOH to dissolve the LA ester, then demethanolize it, hydrolyze it using KOH-distilled water under nitrogen with reflux, then treat with HCl or H2SO4 to get the acid and then convert the iso to the product you need, and finally amidate it using CDI+DBU , chromatographic separation, or use PyBOP, but I rarely see it used around here!
Them: I checked out some of the users of Thevespiary and I found that a lot of people get tar when they use water treatment, perhaps this requires lower temperatures with lower alkali concentrations, you could try it in small amounts
Them: You can try to try using methanol-KOH dissolution then water-KOH reflux, using nitrogen in case it works
Also, in the recent past there have been many new methodologies for the direct conversion of methyl esters to amides.
Me: I’ve heard about this direct conversion but I’ve never heard of it working. What is the process?
Them: It should be an amine ester exchange using DBU and 1-BUOH. In Pfizer's synthesis of Tofacitinib citrate, the last step requires the construction of an amide bond, and DBU-catalyzed amine ester exchange is used.
Them: Org. Lett., Vol. 12, No. 2, 2010, 324-327
Them: Use TMSOK or TMSONa
Substrate and TMSOK 1:1.2, using THF as solvent, you can de-esterify the base at room temperature, adjust the acid to precipitate the product or extract it, the article may be in the journal of Croat.Chem.acta, I forget, if you are interested, look for it, get carboxylic acid and try CDI or CDI+DBU20:02
Them: Hi, sorry to get back to you so late.
I asked my friend but he didn't inform me, maybe for commercial reasons, I guess you can use a methanol solution of KOH to dissolve the LA ester, then demethanolize it, hydrolyze it using KOH-distilled water under nitrogen with reflux, then treat with HCl or H2SO4 to get the acid and then convert the iso to the product you need, and finally amidate it using CDI+DBU , chromatographic separation, or use PyBOP, but I rarely see it used around here!
Them: I checked out some of the users of Thevespiary and I found that a lot of people get tar when they use water treatment, perhaps this requires lower temperatures with lower alkali concentrations, you could try it in small amounts
Them: You can try to try using methanol-KOH dissolution then water-KOH reflux, using nitrogen in case it works
Also, in the recent past there have been many new methodologies for the direct conversion of methyl esters to amides.
Me: I’ve heard about this direct conversion but I’ve never heard of it working. What is the process?
Them: It should be an amine ester exchange using DBU and 1-BUOH. In Pfizer's synthesis of Tofacitinib citrate, the last step requires the construction of an amide bond, and DBU-catalyzed amine ester exchange is used.
Them: Org. Lett., Vol. 12, No. 2, 2010, 324-327
Them: Use TMSOK or TMSONa
Substrate and TMSOK 1:1.2, using THF as solvent, you can de-esterify the base at room temperature, adjust the acid to precipitate the product or extract it, the article may be in the journal of Croat.Chem.acta, I forget, if you are interested, look for it, get carboxylic acid and try CDI or CDI+DBU20:02
- By Blammo
Thank you, this is very interesting info!
I have this link, and it probably is missing little bits that a real chemistry would know to include, but it is a good guideline.
CDI is the way to go, but I do believe it produces iso lsd, so you'd have to use column chromatography to get the lsd with no iso.
I'm surprised CDI isn't sold here, or PyPOB, seems like it'd be a winner. Maybe they do on the darknet or something, haven't looked anywhere like that yet.
I have this link, and it probably is missing little bits that a real chemistry would know to include, but it is a good guideline.
CDI is the way to go, but I do believe it produces iso lsd, so you'd have to use column chromatography to get the lsd with no iso.
I'm surprised CDI isn't sold here, or PyPOB, seems like it'd be a winner. Maybe they do on the darknet or something, haven't looked anywhere like that yet.
