Sciencemadness Discussion Board

Custom Organic Synthesis Costs

BrainAmoeba - 18-5-2021 at 18:12

Hello,

Recently, I have gained some knowledge in topics of organic building blocks design and synthesis planning. I have also discovered that there are many companies that specialize in custom synthesis.

Does anybody know the price ranges of such orders (number of steps, purity, amount and their influence on the cost)?

Sulaiman - 18-5-2021 at 22:02

I have zero experience here but I guess that the cost would be more than buying the required equipment and materials :)

I think that the hard part will verifying the purity of your product, so you may need to pay for analysis (eg gc-ms)

Texium - 19-5-2021 at 06:07

I don’t know much about these companies, but I do work in an academic synthesis lab, so I have an idea of what would likely go into it. I probably spend about 4 to 5 hours of active working time on each step of a synthesis, when you include setup, workup, usually column chromatography, and analysis. Let’s say a synthesis chemist makes about $30 per hour (a lot more than I do as a grad student, but that may even be lowballing it for industry standards). So that’s $120-150 of labor per step of the synthesis. We’ll go with the lower end of that since they’re likely more efficient than I am, but they probably make more money than I estimated. So $120 per step. Reagent cost could be pricey too, depending on what it is you need. The larger amount you need should actually make the price a better deal, considering the labor is the most expensive part, and the work to make 10 grams is the same as it would take to make 0.1 gram. If you need exceptional purity, that would require more labor time, since it would need additional chromatography or other purification techniques, and it would require verification by more analytical methods too. Most research chemicals that aren’t required to be ultra high purity, I’d bet they likely get an NMR and HPLC trace, say “yep, that’s at least 97%” and call it good enough. If you need 99.9% then they’ll probably need to purify it more stringently and use high resolution MS and/or elemental analysis to verify the purity. Put a tidy profit for the company on top of that, and you’ve got yourself one expensive chemical.

I don’t think that there would be any justification for an amateur to order from one of these companies. They cater to companies with big R&D budgets and university labs with lots of grant money (even then, most PIs will likely opt to have their much less expensive grad students make the compounds, even if it takes a little longer). I also don’t think it would be a very easy business to get into, mainly for the need to pay for analysis that Sulaiman mentioned. It would be difficult to make a profit and have timely turnaround on your products if you had to constantly rely on a third party that’s also trying to make a profit to verify the quality of your products.

draculic acid69 - 19-5-2021 at 08:02

China. I don't see how it could be affordable to use such a service with
non Chinese Labor unless you're one of the previously mentioned
Universities or companies with r&d budgets.


[Edited on 19-5-2021 by draculic acid69]

Texium - 19-5-2021 at 08:10

If you need it in large quantity (kilos). If you need it on a gram scale, they probably won’t even acknowledge your request.

Dr.Bob - 19-5-2021 at 09:55

More recently the price for outsourced compounds in the US is $1000 per day of labor plus materials. The $1000 covers labor, overhead, hood space, equipment costs, waste disposal, and much more. Often the cost of chemicals is nearly immaterial, unless you are doing something with pricey chemicals. But once you go to China and do a larger amount, the cost drops to more like $500 to $100 a day as you go larger scale or more compounds.

AvBaeyer - 19-5-2021 at 18:41

I agree with Dr Bob on the daily cost of a "rental chemist." Ten years ago when I was still actively consulting the typical cost of an outsource chemist was figured at $300K per year in the US. This included salary, benefits, supervision, company overhead, and anything else that could be billed. The ten year ago cost is in line with what Dr Bob is quoting for current costs. Chemicals and solvents were extra, usually with a 10% service fee attached. There were/are some contract outfits that will simply resell chemicals from previous projects at full catalog price + service fee. (One of my sons worked for such a company at one time.) Cheaper labor could be found ex-US but project management (and cost control) would be much more difficult, especially with language barriers and time differences.

Texium: The typical synthesis rental chemist (BS level) is billed out at about $150 (or more) per project hour. Contract chemists will typically be working more than one contract project at a time thereby increasing billable hours without actually working extra time. It is how the racket is run. The salary of a good BS-level contract chemist is (now) probably in the $60-75K range. Perhaps Dr Bob has better information.

AvB

[Edited on 20-5-2021 by AvBaeyer]

Texium - 19-5-2021 at 19:26

Well, once I finish my PhD, custom synthesis certainly sounds like it could be a satisfying and lucrative future career for me :D

BrainAmoeba - 25-5-2021 at 17:52

Thanks for all answers.
I've researched the topic a bit more and it looks like a very unaffordable option (maybe bigger customers can afford to do that).

draculic acid69 - 25-5-2021 at 21:32

I seen an article somewhere about someone who contracted a company to make a new compound and they agreed on a price of a few hundred dollars for about five grams or so. So I'm guessing that it's not that expensive if U shop around outside of the u.s

BromicAcid - 26-5-2021 at 02:54

It varies greatly based on the process. Having done my share of quotes, the workflow is something like this:

An experienced chemist who works at the production scale of the process in question evaluates the prep. They look at the process yield, how much material the customer has requested for the quote and determine the scale of the run. Starting material cost is determined and this number goes in the tally.

Based on the prep and the experience of the chemist they determine a rough timeline for running the process i.e., stripping 6L solvent 4 hours, filtration (looks difficult) 6 hours, protracted addition based on reaction temperature (12 hours), overnight stir, 5x solvent exchanges to get DCM content Non-Detect by NMR, etc. (Times are completely made up in the examples here). This helps to determine the timeline.

From the times above, experience comes into play to determine the "hands on" time. Obviously an overnight stir doesn't take 12 hours of a chemist standing over it but a metered addition might take someone standing there baby-sitting it the whole time. So they figure out how much time a person actually needs to spend on the process and then add in a designated buffer (10-20% or whatever) to account for unforeseen difficulties. Then they multiply by the labor rate for the chemist $XXX.XX/hr. Some places will do hood time and not hands-on time so they would just take the previous number for all the operations and multiply it by the time the hood is occupied. Some places do a mix of the two - resource time and hands-on time.

For some processes other factors like waste disposal costs, analytical analysis (multiple NMRs/HPLC/etc), and writing the batch record also come into the cost.

Finally the labor cost, starter cost, and misc. cost are all added up. The customer contract spells out various things, amount they want to purchase and their cost for it, if they are willing to buy surplus material and at what price, delivery due date, purity specs, etc.

A lot of the time custom synthesis in our plant is carried out on small-scale as a means to an end. The process has likely been quoted to run in the 2000 or 4000 Gallon kettles and they want to get the process nailed down at the small scale.

[Edited on 5/26/2021 by BromicAcid]

[Edited on 5/26/2021 by BromicAcid]

Dr.Bob - 26-5-2021 at 11:16

Much of this depends on where you are. A friend has a custom synthesis business in the US, and he is nearly out of work now. He used to get work from many companies, pharma, biotech, and more, but many people would rather buy from Chindia and wait months rather than pay more and get it sooner. Part of the issue is that most (but not all) foreign companies lie about their abilities, delivery time, and purity, and after waiting for months, when the buyer gets less material than promised, at a lower purity and later than expected, they are already late and cannot get their money back, so they make it work.

I have purified materials from overseas before only to be told how much money we saved, and then have management complain that we did not do as much as planned, while ignoring our comments on how much time it took to fix their cheap purchases. So many managers think that they will save money, but ignore the problems and delays when they happen. Much like the people I know that buy tools at Harbor Freight and then complain that they broke or were crap. Used to buy Craftsman tools, back when they were real quality, but now much harder, very few companies make anything in the US, although a few are moving manufacturing back here due to the poor results they got. But in many cases, the prices are so different (from US to overseas source) that no one here can complete.

So if you are in the US, don't think you will make chemicals and earn a living, it is very hard. If you are elsewhere you might be able to do it, but the competition is brutal and mostly on cost, much like EBay or Amazon prices on stuff, cheapest wins.

Praxichys - 27-5-2021 at 13:00

My LLC is a custom synthesis shop and I have reactors up to 50L. I get contracts occasionally but so far it has not been sustainable. It works in my situation because it's just another building on my property so there isn't rent or anything. I really just do it as a side gig that puts maybe $10-20k in my pocket every year.

My younger sister just got a job as a research chemist at a fairly local coatings place. I'm hoping to secure some contracts through that avenue; they have to bid fairly of course but my overhead is so low I can outbid basically anyone.

A good business model today is to get the stuff from China in bulk, certify its purity and purify if necessary, then offer it locally. The margins are small but trust me when I say that I appreciate domestic reagent suppliers and seek product from them first if at all possible.

[Edited on 27-5-2021 by Praxichys]

Fyndium - 27-5-2021 at 14:02

I have been a couple of times in a situation that I needed something RIGHT NOW, not in two months, and was willing to pay a significant premium to whoever supplies it to me as fast as possible.

Do you guys perform only tried synthesis, or do you go on "whatever can be done" basis? How much margin of error do you take on your runs?

zed - 27-5-2021 at 20:06

Well, the first question is: Do you actually need custom synthesis?

Your desired product, or something very much like it, may already be available commercially, at a reasonable price..... Somewhere!

What are you looking for?

BrainAmoeba - 23-10-2021 at 19:44

Hello,

Sorry for being inactive for such a long time.
I am pretty sure that chemical, I was looking for, was not (and is not) available commercially.
Either way, I have solved the problem without custom synthesis which seems to be rather expensive and unreachable (I do not have a company which would help with ordering a custom synthesis itself).

Thank you.

Dr.Bob - 24-10-2021 at 17:50

Quote: Originally posted by Fyndium  
Do you guys perform only tried synthesis, or do you go on "whatever can be done" basis? How much margin of error do you take on your runs?


I currently do contract synthesis type work. We mostly do simple remakes, based on a patent, paper, or other known route. Sometimes we have to scale it up or down some, which can add some extra time to figure out how to make that work, such as checking for exotherms on a scale-up, or how to scale down a route that is in kilos from a patent down to milligrams, as most of the crystallizations in them don't work on small scale well. In those cases we aim at the desired amount or a little higher, and provide whatever we get from the route, sometimes less sometimes a little more than planned.

There are times that someone wants analogs made of a known compound, and then we will do contract to test the route and then have phases where we will make a number of compounds, often based on time and materials, rather than a set price, either making a number with a variable price, or often making as many as we can in a set time and then deciding how many more to make in lots.

Hope that helps. Often things don't work as well as claimed in papers or patents without a few runs to figure out where they left of details, printed the best run of each step, made errors in the written method, or just lied. But often they just leave out many of the details, like how they got seed crystals, the rate of addition, or more useful data.