Scheme 4. Reagents and conditions for the large-scale preparation route of CAT3: (a) Ac2O, Et3N, reflux; (b) FeCl3, m-CPBA, TFA, r.t.; (c) MeOH, H2SO4, reflux; (d) TBSCl, imidazole, DCM, r.t.; 50% in four steps; (e) DIBAL-H, DCM. 0 °C to r.t., 95%; (f) i: NaI, TMSCl, then l-dimethyl glutamate, K2CO3, r.t.; ii: 5% HAc, r.t.; iii: NaOH, CH3OH, r.t., then HCl; 55%; (g) TFAA, r.t., then BF3–Et2O, reflux, 85%; (h) TBSCl, imidazole, DMF, r.t., 85%; (i) NaBH4, DCM-MeOH, then Et3SiH, BF3–Et2O, r.t., 80%; (j) Red-Al, THF, r.t., 95%; (k) pivalic anhydride, Et3N, DMAP, DCM, r.t., 70%.
