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  1. $\ce{Br2/FeBr3}$
  2. $\ce{CH3Cl/AlCl3}$
  3. $\ce{KMnO4}$
  4. $\ce{HNO3/H2SO4}$
  5. $\ce{NBS}$/hv
  6. $\ce{NaOH}$
  7. $\ce{Sn/HCl}$
  8. $\ce{NH4SH}$
  9. $\ce{NaBH4}$

I'm able to get the amino group onto the ring by using 4 and 7. But I have no idea how to get $\ce{-OH}$ in para position (also specify the order).

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I am not happy with the idea of trying to convert a bromobenzene into a phenol using sodium hydroxide. Normally an aryl halide is very inert to nucelophiles, the nitro group will increase the rate but it will not make much difference.

What I would do is to do the following

  1. Nitrate benzene with a mixture of nitric and sulfuric acids to form nitrobenzene

  2. Reduce the nitrobenzene with tin in acid.

  3. To do the synthesis I would want to use nitrous acid and allow the diazonium salt to decompose forming the phenol.

  4. I would nitrate under very gentle conditions to form a mixture of nitrophenols. After separation I would then go to the next step.

  5. I would reduce again with tin in hydrochloric acid to form the target molecule.

I think that a fault exists in the question, I suspect it is an exam question and that the person who wrote the question did a bad job of the question writing.

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  • $\begingroup$ I haven't actually seen SNar with hydroxide but I would have no doubt at all that an alkoxide would do it, this is a key step in the synthesis of fluoxetine. $\endgroup$ – Waylander May 19 '18 at 18:16
  • $\begingroup$ Which step in the synthesis of prozac are you thinking of, I have seen some methods for the synthesis of prozac but I can not recall the route used. $\endgroup$ – Nuclear Chemist May 19 '18 at 18:25
  • $\begingroup$ The SNAr addition of a secondary alkoxide to 4-F-trifluoromethylbenzene. I no longer have Scifinder access so I can't look up an example of hydroxide doing SNAr on 4-Br-nitrobenzene $\endgroup$ – Waylander May 19 '18 at 18:33
  • $\begingroup$ Waylander's answer is also correct.. You can replace Br with OH in brominitrobenzene using NaOH via SNAr mechanism $\endgroup$ – Archer May 19 '18 at 23:33
  • $\begingroup$ Please give a reference to the reaction of hydroxide with an aryl halide to give the phenol. I have checked the literature and Sekar and Thakur in Chem. Commun .,2011,47,6692–6694 were able to get KOH to react with aryl bromides but they used copper and glucose. The fact that they needed to use a transition metal cataylst suggests that the reaction is not a simple nucelophilic attack. Also see International Edition, 2009, vol. 48, # 5, p. 918 - 921 where Pd was used to do the same reaction, it is clearly not a simple nucleophilic attack. $\endgroup$ – Nuclear Chemist May 20 '18 at 5:36
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Steps:

  1. Use $\ce{Br2/FeBr3}$ to make bromobenzene.
  2. Nitrate with $\ce{HNO3/H2SO4}$ to make 4-bromo-nitrobenzene.
  3. Treat with $\ce{NaOH}$ to displace the $\ce{Br}$ making 4-nitrophenol.
  4. Reduce with $\ce{Sn/HCl}$ to make the required p-aminophenol.
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