Trifluoroacetic acid → 4-(4-Iodo-phenyl)-piperidine-4-carbonitrile

HRID 2180161Notes

Reaction equation

HRID 2180161 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11]([C:21]#[N:22])([C:14]2[CH:19]=[CH:18][C:17]([I:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[I:20][C:17]1[CH:18]=[CH:19][C:14]([C:11]2([C:21]#[N:22])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 207794754-Cyano-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 224903724-(4-Iodo-phenyl)-piperidine-4-carbonitrileYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-cyano-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (1.95 g, 4.73 mmol) in CH2Cl2 (37.5 mL) at 0° C. was added TFA (12.5 mL). The mixture was stirred at room temperature for 3 h. TLC (4:1 hexanes/EtOAc) showed no starting material left. The solvent was removed by rotary evaporation and the resulting liquid was evaporated from toluene (2×20 mL), diluted with EtOAc (100 mL) and washed with 10% aqueous NaHCO3 (2×50 mL) and saturated brine (50 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation, dried under high vacuum for 1 h to yield 4-(4-iodo-phenyl)-piperidine-4-carbonitrile as a reddish solid (1.46 g, ˜4.7 mmol, ˜100%). 1H NMR (300 MHz, CDCl3): δ 7.82 (dd, 2H), 7.37 (dd, 2H), 3.25 (m, 4H), 2.15 (m, 4H).

Workup

  1. waitleft
  2. customThe solvent was removed by rotary evaporation
  3. customthe resulting liquid was evaporated from toluene (2×20 mL)
  4. additiondiluted with EtOAc (100 mL)
  5. washwashed with 10% aqueous NaHCO3 (2×50 mL) and saturated brine (50 mL)
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation
  9. customdried under high vacuum for 1 h

Sources & evidence

ORD record
ord-f69cb8ec3d4649af9026680343889306
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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