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How to react 1-bromopentane with diethyl phenylmalonate? I used NaH (1.5eq) but the yield is less than 30%. I used KOH but yield is low. I used tBuOK and it did not work, I used K2CO3, but not working. I tried it, K2CO3 2eq with 18-crown-6 and KI 0.1eq, in acetone but starting material is not consumed, almost only 30% has been finished after more than 72 hours and TLC shows a different spot, it does not look like desired product. Starting material is recovering when I use K2CO3, but not in case of NaH 1.5eq with DMF or THF but yield is less than 30%. Toluene with NaH under reflux condition is also behaving like K2CO3 and my next step is hydrolysis and decarboxylation. I need guideline about what I am missing here.

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  • $\begingroup$ Ethoxide in ethanol would work $\endgroup$ – Waylander Dec 19 '18 at 8:13
  • $\begingroup$ i used NaH(1.5eq) but yeild is less then 30. $\endgroup$ – Dr.usama farooq Dec 20 '18 at 0:08
  • $\begingroup$ i used KOH but yeild is low. i used tBuOK not work, i used K2CO3, but not working $\endgroup$ – Dr.usama farooq Dec 20 '18 at 0:27
  • $\begingroup$ Are you recovering starting material? K2CO3 in MeCN with some added KI is worth trying $\endgroup$ – Waylander Dec 20 '18 at 8:09
  • $\begingroup$ i tried it, K2CO3 2eq with 18-crown-6 and KI 0.1eq, in acetone but starting material is not going to consume, almost only 30% hasbeen finished after more then 72hours and TLC shows a different point, its not looks like desired product. $\endgroup$ – Dr.usama farooq Dec 20 '18 at 9:00
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You have tried a number of sensible approaches and nothing is working well. I think the problem here is that the anion you are creating is very stable and hindered and no amount of tweaking will significantly improve it. You either accept the yield as it is and scale the reaction accordingly, or change your strategy.

Your next step is hydrolysis and decarboxylation to give a substituted phenylacetic acid so I suggest you start with ethyl phenylacetate. You could alkylate it with NaH (1eq) in DMF with KI then 1-bromopentane. That should alkylate well, but there will be a percentage of di-alkylation so I'm going to suggest you condense ethyl phenylacetate with pentanal and then hydrogenate (or otherwise reduce the double bond). I think this will give you a cleaner reaction mixture and higher yield.

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  • $\begingroup$ Thank you so much for your kind suggestions. . $\endgroup$ – Dr.usama farooq Dec 21 '18 at 2:40

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