December 12, 2019, 02:57:41 AM
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Topic: Help with Mitsunobu reaction  (Read 1957 times)

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Offline Pandelev

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Help with Mitsunobu reaction
« on: March 09, 2018, 02:22:35 PM »
Hi everyone,
I have a problem with a mitsunobu reaction.
I'm trying to make the ether of 2-amino-4-hydroxyquinoline with N-Boc-ethanolamine.
I have mixed 2-amino-4-hydroxyquinoline, PPh3 and ethanolamine to freshly distilled THF (2 mL, 0.3M solution of quinoline). After cooling to 0°C I added DIAD under argon. The suspension (the quinoline seems to be insoluble in THF) was stirred for 3days, but I cannot find any trace of products, analysis was made by reverse phase LC-MS.
Any suggestion?

Offline kriggy

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Re: Help with Mitsunobu reaction
« Reply #1 on: March 09, 2018, 04:30:41 PM »
Few things you can try:
a) try to first mix PPh3 with DIAD then add alcohol, let it mix for shor time and then add into the quinoline (order of addition matters in this reaction)
b) try different solvents (dioxane, toluene, DCM)
c) try other azo compounds (DEAD for example)

Offline OrganicDan96

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Re: Help with Mitsunobu reaction
« Reply #2 on: March 09, 2018, 07:49:30 PM »
c) try other azo compounds (DEAD for example)

DEAD is really hard to get hold of and dangerous (like the name suggests). there are many others like the piperidine derivative (which works better for less acidic acids).

you could also try different phosphines like tricyclohexyl phosphine

mitsonobu reactions vary massively according to substrate so you will probably have to try many different iterations before it will work properly. 

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