Trifluoroacetic acid → 3-Amino-4-chloro-5-(3-fluoro-3-azetidinyl)benzonitrile

HRID 921893Notes

Reaction equation

HRID 921893 reaction equation
C(OC([N:8](CC1C=CC(OC)=CC=1)[C:9]1[C:10]([Cl:29])=[C:11]([C:17]2([F:28])[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]2)[CH:12]=[C:13]([C:15]#[N:16])[CH:14]=1)=O)(C)(C)C.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[CH:14]=[C:13]([CH:12]=[C:11]([C:17]2([F:28])[CH2:18][NH:19][CH2:20]2)[C:10]=1[Cl:29])[C:15]#[N:16]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 118253466HCID 118253466, compound

Product 1

HCID 899225193-Amino-4-chloro-5-(3-fluoro-3-azetidinyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 3-(3-((tert-butoxycarbonyl)(4-methoxybenzyl)amino)-2-chloro-5-cyanophenyl)-3-fluoroazetidine-1-carboxylate, (Example 658B) (321 mg) in DCM (15 ml) was added anisole (0.5 mL, 4.52 mmol), followed by TFA (7 ml). The resulting mixture was stirred at room temperature overnight. Solvent was removed. The residue was taken in MeOH and applied onto a cartridge of Phenomenex Strata-X-C 33 um cation mixed-mode polymer. This was washed with methanol and the product was eluted with 2 N solution of ammonia in methanol. Removal of the solvents left 3-amino-4-chloro-5-(3-fluoroazetidin-3-yl)benzonitrile (127 mg) as a solid.

Workup

  1. customSolvent was removed
  2. additionmixed-mode polymer
  3. washThis was washed with methanol
  4. washthe product was eluted with 2 N solution of ammonia in methanol
  5. customRemoval of the solvents
  6. waitleft 3-amino-4-chloro-5-(3-fluoroazetidin-3-yl)benzonitrile (127 mg) as a solid

Sources & evidence

ORD record
ord-67ad587018514b2e9c93e5b115166e86
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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