Comments on: 4-(2′-bromoethyl)-3-chloro-2-inolinone from isochromane

By: OrganicOverdose

OrganicOverdose — Wed, 10 Mar 2010 04:28:54 +0000

Hey Milkshake,
Have been glad to hear from you more often of late. Happy belated b’day. That is some funky chemistry you posted with a interesting rearrangement. Some mechanisms on this would be interesting. Also, in reference to that student post about DCC, surely using a different activating reagent, even EDC would be the best option. Although, of late biphasic mixtures or suspended reactions have taken my interest as well. Sometimes even water sensitive reactions being done in biphasic reactions (H2O/DCM or Toluene) have proven successful.

By: milkshake

milkshake — Sat, 06 Mar 2010 23:24:47 +0000

Thank you for the well wishes but I would rather be an elephant – one that comes to a village at night to soak from their barrels of rice beer

By: parit

parit — Sat, 06 Mar 2010 18:19:56 +0000

hey milkshake,

i am a ghost reader for while for your blog. I m deeply sorry for what you are going through. But remember one thing ‘ In this great jungle, mighty lion sleeps happy every night. Great lion is not. So, i strongly suggest that you should try to be might lion not great lion for a while’. Also, Everything happens for our good. Peace.
parit.

By: milkshake

milkshake — Fri, 26 Feb 2010 13:25:46 +0000

I forgot to mention: after I did the FeCl3-AcCl cyclization and got my product in not-so-great yield, I was curious where the remaining mass balance went so I columned the supernatants and isolated the main sideproduct. I did not manage to figure out what was it but it had the alpha chlorophenacetic portion, bromoethyl and AcONH in the molecule. And it was oily – definitely not an oxindole. It looked like non-cyclized product on NMR

By: milkshake

milkshake — Fri, 26 Feb 2010 13:20:19 +0000

it is actually from a ropinirole process paper. Eventually they run into bromide elimination problem with dipropylamine as a nucleophile (n-Pr2NH is a somewhat hindered amine) so they re-did the synthesis with benzoyloxy and tosylated in the end, and turns out tosyl does not eliminate nearly as much as bromo. But making the tosyl analog is steppier – first they open the ring of isochromane with PhCOCl and ZnCl2, then they do Sommelet oxidation on the obtained benzyl chloride, etc.

By: andrew

andrew — Fri, 26 Feb 2010 12:09:03 +0000

Milkshake,
This reminded me of the synthesis of ropinerole stage 2. I can no longer get at the data on this and the Publications are behind paywalls. Ropinerole stage 1 is the synthesis of the nitrostyrene, stage 2 the Ferric chloride cyclisation, the quality of the ferric chloride is critical for yield and reaction time, the latter varying from ~5 hrs to oner 24 hrs

By: milkshake

milkshake — Thu, 25 Feb 2010 19:00:17 +0000

thank you. I should know soon what my job situation will be like, lets hope that I will end up swamped too

By: Rhenium

Rhenium — Thu, 25 Feb 2010 18:22:01 +0000

Yay! The offer is still very much there, I have just been swamped of late. There is a potential NSF inorganic workshop in mid-May in Santa Fe and then I’m off home for a month, but early May will be a perfect time.

By: psi*psi

psi*psi — Mon, 22 Feb 2010 05:37:13 +0000

mmm. I bet May is a nice time for you, too, to get out of the humidity

By: milkshake

milkshake — Sun, 21 Feb 2010 21:12:27 +0000

Thank you Jes, really. I wish I was somewhere completely else. If there is time – and if some mundane things like a job search do not interfere – maybe I will go to see Rhenium in Flagstaff this May because I have bunch of friends in Tucson and I miss them (and Arizona desert too) and the two places are within a driving distance, so I could combine the visit.