4-Fluoro-2-(trifluoromethyl)benzonitrile → HCID 18700146, compound

HRID 2289306Notes

Reaction equation

HRID 2289306 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].F[C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([C:30]([F:33])([F:32])[F:31])[CH:23]=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([C:30]([F:31])([F:33])[F:32])[CH:23]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6050854-Fluoro-2-(trifluoromethyl)benzonitrileHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 18700146HCID 18700146, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of N-tert-butyloxycarbonyl-4-piperidinol (1.0 g, 5.0 mmol) in THF (20 mL) at 0° C. was added potassium tert-butoxide (5.0 mL of a 1.0 M solution in THF, 5.0 mmol). The mixture was stirred for 10 min and 4-fluoro-2-trifluoromethyl-benzonitrile (1.04 g, 5.5 mmol) was added. The mixture was stirred at 0° C. for 1 h and then at ambient temperature for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 (50 mL). The organic phase was dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 1:2 EtOAc:hexanes as eluant to give 4-(N-tert-butyloxycarbonyl-4-piperidinyloxy)-2-trifluoromethylbenzonitrile as a colorless gum.

Workup

  1. stirringThe mixture was stirred at 0° C. for 1 h
  2. waitat ambient temperature for 14 h
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was partitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 (50 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by pressurized silica gel column chromatography

Sources & evidence

ORD record
ord-ddb9bb0a0e8a4f2ba430c7cded9eef2a
Source dataset
uspto-grants-2000_07
Patent number
US06090805

Reaction notes

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