[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[CH:11]2[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.[ClH:31].CCCCCC>C(Cl)Cl>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:4][CH:3]=1.[ClH:31]
To a solution of tert-butyl 4-(6-fluoroindolin-1-yl)piperidine-1-carboxylate prepared as in STEP 1 above (16.64 g, 52 mmol) in CH2Cl2 (45 mL) was added TFA (30 mL) slowly at room temperature. The resulting mixture was stirred at room temperature for 3 h (monitor by HPLC). The resulting mixture was then concentrated to remove most of the solvent and TFA. The resulting residue was partitioned in CH2Cl2/H2O (100 mL/50 mL) and stirred. 3N NaOH(aq) was then added slowly until the pH value of aqueous layer was >11. The aqueous layer was then extracted with CH2Cl2 (100 mL×10). The combined CH2Cl2 layer was dried (Na2SO4) and filtered. The solvent was removed and the resulting residue was dissolved in Et2O (100 mL) and then 1N HCl (1M in Et2O, 60 mL, 60 mmol) was added slowly at 0° C. The resulting mixture was allowed to warm to room temperature for another 30 min. Hexane (100 mL) was added and the resulting mixture was stirred for 15 min. The resulting white solid was filtered and washed with 50% Et2O/hexane (30 mL×3), then dried to yield 6-fluoro-1-(piperidin-4-yl)indoline as a white HCl salt.
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