Extracting the quoted strings and then searching for them again is kind of inefficient. Likewise for having to create a new regexp for every single quoted string. Perl goes to a fair amount of trouble to compile a regexp into something that walks through a string; the whole point of that is so that you can re-use that walk routine lots of times.

Meaning what you really want is a single regexp fixed in advance that gets applied to every line. Bonus points if you can have it be a walk-thingie that only has to do a single pass through the string (which then means you want to think about how you'd do the walk if you had to do it yourself). Try this

use strict; use warnings;

while ( my $line = <DATA> )
{
   print "# ORIG: $line";

   if ($line =~ m/"/g) {
      $line =~ s/\G([^,"]*(?:"[^"]*"[^",]*)*),/$1|/g;
   }

   print "#  NEW: $line";
}

__DATA__
ONE,"TWo,2",Three,Four,Five
ONE,"$TWo,2",Three,Four,"Fi,ve,,"
ONE,"$TWo2","Three,(3)",Four,Five
ONE,"$TWo2","Three,(3",Four,Five
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