4-(Trifluoromethyl)phenylacetonitrile → Tert-butyl 4-(cyano(4-(trifluoromethyl)phenyl)methylene)piperidine-1-carboxylate

HRID 632721Notes

Reaction equation

HRID 632721 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1.[O-]CC.[Na+].[C:18]([N:25]1[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C(O)C>[C:10]([C:9]([C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:12])([F:13])[F:1])=[CH:8][CH:7]=1)=[C:28]1[CH2:29][CH2:30][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:26][CH2:27]1)#[N:11]

Participants

5

Reactant 3

HCID 753594-(Trifluoromethyl)phenylacetonitrileHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2723922Sodium ethoxide

Product 1

HCID 118046949Tert-butyl 4-(cyano(4-(trifluoromethyl)phenyl)methylene)piperidine-1-carboxylateYield 66.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

To the solution of 4-(trifluoromethyl)phenylacetonitrile (2560.9 mg; 13.83 mmol; 1.06 eq.) in ethanol (50 mL), 21% sodium ethoxide (5.70 ml; 15.27 mmol; 1.17 eq.) in ethanol was added dropwise at RT. After stirred for 30 min, a solution of 1-boc-4-piperidone (2600.00 mg; 13.05 mmol; 1.00 eq.) in ethanol (10 mL) was added slowly. The reaction mixture was stirred at room temperature for 4 h. The reaction was quenched with 50 mL of saturated aqueous NH4Cl and concentrated to half volume. The aqueous solution was extracted with ether three times. The combined organic extracts were washed with brine, dried and then concentrated to give the crude product, which was purified by Biotage chromatography with EtOAc/Hexane (5-30%) to yield the desired product as light yellow solid (3200.00 mg, yield 66.9%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 4 h
  2. customThe reaction was quenched with 50 mL of saturated aqueous NH4Cl
  3. concentrationconcentrated to half volume
  4. extractionThe aqueous solution was extracted with ether three times
  5. washThe combined organic extracts were washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by Biotage chromatography with EtOAc/Hexane (5-30%)

Sources & evidence

ORD record
ord-8e23a718c5b746f79dc28a1456aa1bea
Source dataset
uspto-grants-2016_04
Patent number
US09321760B2

Reaction notes

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