Hey F42k/GLG Fam,
Attached is my CBD-D8 Master SOP. 10-20Kg Scale, 100L Reactor.
@Future
Gang gang,
ILL
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very well written SOP! ill read it shortly and give my opinion
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Do you find it cumbersome to weigh out and then melt the CBD? Could you not charge your solvent, get it stirring at low RPM with gentle heat (like 40-50C on the jacket side, maybe 30-35C internal) and then just add the CBD as a solid? That’s sort of rhetorical, in that I already have charged solids this way and it works - but I guess my real question is there a reason you prefer this method? The additional of solid CBD does provide some amount of cooling in and of itself. I guess one drawback is that, unless you’re at reflux, you may have solid CBD hanging around the top of your reactor.
I hate charging solids as much as anyone else, and I know its not great form to open a reactor manway above the flash point…but with inert gas, grounding, and good ventilation I don’t think the risk is very great under 40C. Drawbacks I see to melting CBD are: time, carrying/pouring a hot liquid, errors in mass from transfer containers not pouring 100% dry, only being able to heat up a few kg at a time per container (larger containers suffer from reduced heat transfer). Any thoughts?
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I agree with your methodology. Whichever you prefer to get the CBD and Heptane to fully homogenize. I usually just dump in 10-20kg’s at night. Come back in the shop in the am, turn on my reactor, go handle a few things in the lab, then come back for Solvent addition.
The key here is to ensure that your solution is fully homogenized and no greater than 50c before the addition of the acid. Temp increases 10-30c upon addition of PTSA and it’s gotten pretty sketchy if I’m rushing. As long as your solution is homogenized, and temp is stable before addition of acid… you’re good to go. 
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i find for d9 synths particularly that pumping in molten CBD is more ideal then opening up the addition portal and adding it in that way; your not compromising the integrity of your inertness as much via a liquid addition.
for d8 tho its a bit overkill; imo; and a huge time sink; youll need to start preping the night before in order to make sure everything is ready to go; not a big deal tho; just pot it up and throw it in the oven overnight.
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I see nothing wrong with this method; its well written; beautifully organized. i would run this method myself.
i really really like the flow diagram; it lays out the order of operations very well; and makes the entire process easy to do.
@iLLnyeTheShatterGuy very well done; 9/10 youd get a 10/10 if you didnt miss spell “CONGRADULATIONS” at the end of the SOP. just joking gotta give you a hard time about something at least 
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Oh, I know a thing or two about sketchy exotherms - I bring them up like a broken record because I’m very very familiar with this reaction. What you’re alluding to as sketchy, I am acquainted with. Up until recently, there was an operator in the same facility as me running these reactions fast and loose and he blew up the reactor a good number of times. Unfortunately, there was nothing I could do to influence the safety culture at that organization.
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expand on this? let me guess; he made the acidic addition when the system is at an elevated temp?
edit: misread
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Hahahaha awe Shit. Looking at screens for too long 
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what I described in the other post - the azeotropic drying procedure. You can charge your solvent wet (I prefer to dry my solvent beforehand, but I think you see my point), charge your CBD as a solid, and azeotrope the whole solution before adding any reagents. That way, it doesn’t matter how wet the CBD you bought was. I think many of us acknowledge we don’t know how much water is retained in the CBD we buy, and drying the whole solution is a good way to expel unforeseeable water from the substrate itself before running a reaction. Just some food for thought.
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oh you know - basically doing every dangerous possible combination. Running the reaction with not enough solvent to absorb the exotherm…running the reaction in solvents with boiling points too low to absorb the exotherm…running the reaction with 3-10x the necessary acid…forgetting to turn on argon gas or ventilation…beginning the additions at elevated temperatures…evolving vapor so quickly the glass reactor is pressurized…filling the reactor way too high to accommodate vigorous reflux…not telling anyone when he was charging the acid so you’d turn around randomly to find your in the same room as a runaway reaction. I would find this kid, with no PPE, looking at the reactor from a few feet away as its clearly reaching criticality not even comprehending the dangerous situation unfolding before him…and like bum rushing him out the door in case it blew up. Motherfucker had no idea he was inches away from needing a skin graft, on multiple occasions, and that I had knowingly put myself in harms way to keep him safe.
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Revised and uploaded. Do I get a 10/10 ??
Yeah, I love the flowcharts. Makes it very easy for technicians to visually grasp the process as a whole.
Check out LucidCharts online. Free and dope.
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Thank you brother Thanks for being a part of our badass community!!
#leveluptogether
We will be releasing a ton of our Master SOP’s for GoodLifeGang Certification (GLGc) here shortly. All will be FREE as well.
@Future
32 Likes
My only question would be the stir RPM. Do you observe that going higher than 100RPM doesn’t help with mixing during the washes?
Also, in the Procedure, Reaction section it says to add acid by volume but then it quotes a mass figure. Clarity at that step will make it easier to repeat
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Good call out. 1% by mass of CBD.
1% of 10,000g’s of CBD = 100g’s of pTsOH
Scalable up to 20,000G’s/20kg’s… same parameters. For this reactor method. I normally run 20Kg batches.
Washes/Rpm’s:
I haven’t done any actual experimentation as to the correlation of rpm’s and homogenization for this method. I’ve just always done a slow and steady method with washes. Kinda just took the ideology of doing LLE in a sep funnel. So going to a reactor… obviously much better homogenization compared to a hand agitation of a sep funnel and off gas via stopcock. Getting a new HPLC in a few weeks and would be interested in taking some intermediates at different rpm’s to see if there’s a difference. What’s your thoughts on it? Higher rpm’s better homogenization? That would definitely be logical, just not sure if it needs a super vigorous mix. 
I try to not change too many parameters at once to keep things smooth and accurate throughout. That way I can diagnose a problem quickly if something changes within the reaction. Specially with the washes and neutralizing the pH. Neutral pH is crucial when it comes to the distillation end of this process.
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A quick test would be to turn up the stir to max after your last wash to see if it changes the pH of the water.
In my experience shaking a sep funnel will generally cause more vigorous mixing than a 100RPM stir
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