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june 2007 org prep daily org prep daily june 30 2007 base baths filed under uncategorized milkshake 3 59 pm the classic soak bath is a mix of isopropyl alcohol with a generous amount of concentrated aqueous koh the disadvantage is that is tends to evaporate over time is flammable and it shouldn t be poured in the sink because epa can bust you for sending isopropanol down the drain there is one good base bath alternative without isopropanol that contains aqueous koh with k3po4 or any other k phosphate with extra koh to make stuff strongly basic mixed with some diluted liquid anionic household or laundry detergent a common grade based on greasy chain sulfonic acids works best the foaming is not much of a problem if you don t overdo it with the detergent few spoons is enough for a bucket please note that na phosphates or naoh cannot be used as a substitute because na3po4 hydrate is poorly soluble and crashes out of the mix also some weird detergents tend to form an oily layer if the mix is too concentrated and salty on the first try one should test the compatibility of the detergent before mixing vats of the bath solution this phosphate based alkaline bath without iproh works very nicely for an overnight soak and i would encourage all alkaline bath lovers to give it a try ____________________________________________________________ i wash my dirty glassware as soon as it is produced it is much easier to wash before the stuff dries on i prefer doing fewer experiments in parallel but clean and wash inbetween so that at the end of the day the hood is nice and organized again and cleared of the clutter hot water and acetone mostly does it for me for difficult cases the bottles with 2m naoh 6m hcl and dmf are at hand the particularly nasty pieces of glassware are saved until i feel brave enough to play with piranha mix i stopped using base baths because they take space and i don t like to fish in a bucket full of slippery glassware soaking in a caustic mix aluminum parts and frited funnels are eaten in base baths and the forgotten pieces of the glassware are slowly etched but if you want your flasks picture pretty then base bath is the way to go update the actual ratio for a large base bath tank that holds approx 100 liters of of solution is 1 kilo of common grade 85 koh pellets dissolved in about 2 liters of water add 250g of k3po4 in about 2 liters of water dilute up to 100 liters total volume then add a whole bottle of liquid non scented color free laundry detergent containing 32 laundry loads we use a publix grocery store free and clear brand with a little dirty boy on the bottle it is supposed to contain a mix of anionic and non ionogenic detergents and costs about 3 a bottle comments 32 june 29 2007 patentz filed under industry life milkshake 11 16 am credit jiri sliva i have gone on a tirade here about how writing your own patents is insidious because one gets encouraged by the demons in his head the management and the patent lawyers to fudge things a bit and that s exactly how some medicinal chemists start cheating i deleted that piece because it wasn t written well i may come back to the subject when i calm down though i should explain now what set me off to ramble about these things i submitted a bunch of experimental procedures for a patent application in which i was the sole person doing the synthetic work after the provisional patent was issued i found out that two fictitious experimental procedures were included in the patent submission our patent lawyers found it expedient to dream them up when i protested the lawyers explained to me that they really didn t have to tell me and i shouldn t worry about such additions because they are being done by experts from the lively debate that ensued i learned that i was using incorrect english what i call a fake experimental procedure is actually a prophetic example what i call bullshit is a modus operandi i think it is reasuring to find the lawyer jokes so accurate comments 9 june 26 2007 faked experiments filed under industry life milkshake 3 41 pm when i came to us to join a small startup biotech company my first assignment was to re synthesize an active literature compound a repulsive looking peptidomimetic macrocycle the compound was to be used in validating a new bioassay the father of our young ceo needed the compound for his academic research our company initiated a collaboration with his group and that meant somebody ought to synthesize the stuff nobody volunteered but i was new and couldn t protest and my boss gushed that i could deliver the compound in six weeks it took me over six moths of a full time work i was repeatedly offered reassignment to another project but i refused since i did not like to admit a failure the synlet paper describing the synthesis that i was supposed to reproduce had no experimental procedures and the used starting material was not commercial or described in the literature the only procedure for the starting material was in the phd thesis of a person who did also the work on this published macrocycle the procedures in the thesis were rather vague they never worked in my hands or in the hands of another chemist i soon noticed that a hydrolytically unstable silylated amine intermediate in the first step of a multistep sequence was formed in less than 50 nmr yield under conditions described in the thesis and the entire material was then immediately decomposed if the workup specified in the thesis was used so i obtained this sensitive intermediate by alternate procedure purified it by kugelrohr distillation and took it to the next step which also failed eventually i realized that the irreproducible thesis procedures were meant to be a simplified version of a known synthetic sequence this original unmodified sequence worked exactly just as described so i changed the protecting groups on the material in the end and then i could proceed with making the actual macrocycle i had a number of unpleasant surprises following the scheme and finally the key condensation reaction did not work at all the reagents they used in the published scheme were different from the lit reference that they gave as a precedent for this step and neither of these methods gave any trace of the desired product on many attempts i was getting desperate eventually i found a synthetic chemist whom i could talk to from the group that published this irreproducible stuff as i was describing my troubles he was laughing it turns out that what they published was apparently an unmodified synthetic scheme from some grant proposal with made up yields they never retracted anything even after i alerted the pi about the problem and they kept re publishing this mess once in pnas then synlett and later i think in chem rev my inside friend told me what kind of method they would use in such a case different from the one published so i was able to complete the molecule convince my superiors that the problem was with the published baloney rather than with my freshly minted ms degree from eastern europe looking back i think the pi in question knew from the beginning that his published work was irreproducible but he could not afford to retract because he had to keep hyping the technology platform of his troubled small company in order to make the investors to continue pouring money in he also tried to plagiarize our methodology i carelessly talked about my unpublished work and he published our results as his own cordova style his company folded in the end credit jiri sliva comments 7 june 25 2007 5 bromofurane 2 sulfinic acid lithium salt filed under procedures milkshake 10 55 pm 2 5 dibromofurane 1 570g tci us 6 95 mmol solution in anh thf 15ml was cooled under ar to 78c and buli 2 5m solution in hexanes 2 6ml 6 50 mmol was added dropwise over 8 min period the mixture was stirred for additional 15 min then quenched at 78c with a stream of sulfur dioxide gas aldrich lecture bottle above the reaction mixture level for about 10 min the volume of reaction mix increased by about 8 ml the cooling bath was removed and the excess of condensed so2 was blown off with a stream of ar gas about 30 min at rt the reaction mixture was portioned between water 100ml and hexanes 100ml the organic phase was re extracted with additional water 2x25ml the aqueous extracts were washed with additional hexanes 40ml the aqueous extracts were combined and evaporated the obtained solid residue was dried on highvac y 1 274g 90 th of a light tan semicrystalline solid approx 95 pure by nmr hplc 1h d6 dmso 400mhz 6 430 d 3 2hz 1h 6 276 d 3 2hz 1h 13c d6 dmso 100mhz 172 38 119 89 111 68 107 79 lc ms esi 209 211 comments 5 june 22 2007 direct preparation of 2 aminopyridines from pyridine n oxides filed under lit highlights milkshake 6 54 pm there is a lovely joc note from merck process group the n oxide is transformed to n tert butylamino intermediate and then deprotected in situ with tfa in a one pot operation the procedure works well with a wide variety of substrates pyridines quinolines isoquinolines the few examples of unsymmetrically substituted pyridine oxides that had both the 2 and 6 positions free provided a mix of the two ortho amino regioisomers this is an improved version of the amination procedure with tscl nh3 that was useful for 2 aminoquinoline scale up couturier et al org process r d 10 2006 534 8 another related simple procedure for acylamidation of n oxides from pfizer process group uses rconco that is generated generated in situ from rconh2 and oxalyl chloride this acylamination procedure is however limited to quinolines isoquinolines and phenanthrolines pyridine n oxides fail in the acylamidation comments 10 june 17 2007 new reactions from carreira filed under lit highlights milkshake 5 52 pm a fundamentally useful addition reaction that gives good yields with variety of substrates in ethanol at room temperature on a gram scale markovnikov product no stereoselectivity with chiral substrates no ee s reported with jacobsen co salene as a catalyst so probably there aren t any the catalysts are either commercial or 1 step to make the azides can be transformed to triazoles or amines in situ works great with safrole comments 17 older posts pages about milkshake about org prep daily bug report chemistry resources chemistry chemjobber in the pipeline med chemist open flask org chem portal practical fragments stellen fuer chemiker edible links serious eats links to behold idle words categories chris douglas industry life krest17 lab destruction lit highlights mechanisms procedures questions uncategorized search archives january 2026 december 2025 november 2025 october 2025 september 2025 april 2019 march 2019 december 2018 june 2018 september 2017 august 2017 march 2016 october 2015 august 2015 july 2015 june 2015 march 2015 november 2014 july 2014 may 2014 september 2013 july 2013 may 2013 april 2013 october 2012 september 2012 august 2012 january 2012 december 2011 november 2011 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