Potassium Carbonate → 1-{4-[(1E)-pent-1-en-1-yl]phenyl}cyclohexanecarbonitrile

HRID 2090098Notes

Reaction equation

HRID 2090098 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH:16](B(O)O)=[CH:17][CH2:18][CH2:19][CH3:20].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CCOC(C)=O.C([O-])(O)=O.[Na+].[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[CH:16](/[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:14][NH2:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1)=[CH:17]\[CH2:18][CH2:19][CH3:20].[CH:16](/[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1)=[CH:17]\[CH2:18][CH2:19][CH3:20]

Participants

9

Reactant 3

HCID 11430Potassium CarbonateHCID 1166131-(4-Chlorophenyl)cyclohexanecarbonitrileHCID 27346091-Pentenylboronic acid

Product 2

HCID 594359221-(1-{4-[(1E)-Pent-1-en-1-yl]phenyl}cyclohexyl)methanamineHCID 684116391-{4-[(1E)-pent-1-en-1-yl]phenyl}cyclohexanecarbonitrileYield 144.2%

Reagents, catalysts & solvents 4

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of 1-(4-chlorophenyl)-1-cyclohexanecarbonitrile (100 mg, 0.455 mmol) and 1-pentenylboronic acid (104 mg, 0.910 mmol) in tetrahydrofuran (2 ml) and 1 M potassium carbonate (1.5 ml, 1.500 mmol) was added 1,1′-bis(di t-butylphosphino)ferrocene palladium dichloride (10 mg, 0.056 mmol). The mixture was microwaved at 100° C. in a sealed tube for 20 min, at which point LC/MS analysis showed a new peak. The reaction mixture was diluted with 10 mL of EtOAc and 10 mL of saturated aqueous NaHCO3. The phases were separated and the aqueous phase was extracted with 10 mL of EtOAc. The combined organics were washed with 10 mL of brine, dried (Na2SO4), and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 25M column, eluting with 1 CV of 100% hexanes followed by a gradient of 0 to 100% EtOAc in hexanes over 10 CV to provide the desired product 1-{4-[(1E)-pent-1-en-1-yl]phenyl}cyclohexanecarbonitrile (83 mg, 0.328 mmol, 72.0% yield). To a 0° C. solution of 1-{4-[(1E)-pent-1-en-1-yl]phenyl}cyclohexanecarbonitrile (75 mg, 0.296 mmol) in tetrahydrofuran (2 ml) was added 1.0 M lithium aluminum hydride in ether (1 ml, 1.000 mmol). The mixture was allowed to warm to room temperature and stirred at this temperature overnight, at which point LC/MS analysis showed complete disappearance of the starting nitrile. The mixture was recooled to 0° C. and quenched by dropwise addition of 30 μl of water, 30 μl of 15% NaOH, and 80 μl of water. The mixture was stirred for 30 min at room temperature, and then filtered, washing the solids liberally with ether. The filtrate was concentrated to provide the title compound (78 mg, 0.303 mmol, 102% yield). Mass spectrum (ESI) 258.0 (M+1).

Workup

  1. customThe mixture was microwaved at 100° C. in a sealed tube for 20 min, at which point LC/MS analysis
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with 10 mL of EtOAc
  4. washThe combined organics were washed with 10 mL of brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on a Biotage Horizon, 25M column
  8. washeluting with 1 CV of 100% hexanes

Sources & evidence

ORD record
ord-f3b5e9eba3aa479f8e4f3c364b639217
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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