Synthesis Golf IX: Tezacaftor
I am really glad that you are reviving these challenge questions NotEvans.
As for the synthesis, the amide disconnection leading to fragments A and B seems like the most simplifying first disconnection:

Synthesis of fragments A and B is outlined below:



Esterification of the readily available acid with isopropyl alcohol under Yamaguchi conditions;
Demethylation (this is why I've chosen to make the isopropyl ester, it shouldn't be destroyed with $\ce{BBr3}$);
Formation of a thiocarbonate crucial for the introduction of two fluorine atoms;
JACS 2010, 132(51), 18199;
Aldol condensation of the ester with formaldehyde;
Ester hydrolysis;
Conversion of the acid to acyl chloride.





p-Nitroaniline is brominated;
Sonogashira coupling;
Gold-catalyzed hydroamination;
Fmoc protection of the indole nitrogen turned out to be necessary at this point (so it doesn't interfere with the coupling with fragment A);
Reduction of the nitro group.


Now comes the endgame:




Amide formation;
Corey-Chaykovsky reaction of a stabilized sulfure ylide is selective for enone-like systems;
Piperidine removes Fmoc;
The indole nitrogen attacks glycidol thus opening the epoxide on the more accessible site;
Reduction of the ester with $\ce{LiBH4}$ should be selective. Several equivalents are needed because of the free hydroxyl groups. My only concern is the stability of the cyclopropane, but other hydride donors could be tried.


EDIT: Here is the synthesis of the alkynyl ester needed to make fragment B:

18. Methylacetoacetate is methylated twice;


Formation of enol triflate;
Base-induced elimination of the triflate gives the ester.



  Total step count: 20
  
  Longest linear sequence: 12