Hydrochloric Acid → Hydrochloric Acid

To a solution of tert-butyl 4-(6-fluoroindolin-1-yl)piperidine-1-carboxylate (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. The resulting mixture was concentrated to remove most of solvent and TFA. The resulting residue was partitioned in CH2Cl2/H2O (100 mL/50 mL) and stirred. 3N NaOH(aq) was 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 by roto-evaporator, the resulting residue was dissolved in Et2O (100 mL) and 1N HCl (1M in Et2O, 60 mL, 60 mmol) was added slowly at 0° C. Then, the resulting mixture was allowed to warm to room temperature for another 30 min. Hexane (100 mL) was added and 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.

1. concentrationThe resulting mixture was concentrated
2. customto remove most of solvent and TFA
3. customThe resulting residue was partitioned in CH2Cl2/H2O (100 mL/50 mL)
4. stirringstirred
5. addition3N NaOH(aq) was added slowly until the pH value of aqueous layer
6. extractionThe aqueous layer was then extracted with CH2Cl2 (100 mL×10)
7. dry with materialThe combined CH2Cl2 layer was dried (Na2SO4)
8. filtrationfiltered
9. customThe solvent was removed by roto-evaporator
10. dissolutionthe resulting residue was dissolved in Et2O (100 mL)
11. temperatureto warm to room temperature for another 30 min
12. stirringstirred for 15 min
13. filtrationThe resulting white solid was filtered
14. washwashed with 50% Et2O/hexane (30 mL×3)
15. customdried

ORD-Eintrag

ord-190dc9512be14a81b03f30338c7d34ce

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09238658B2