Diisopropylethylamine → 4-(8-Azabicyclo[3.2.1]oct-8-yl)-3-fluorobenzonitrile

HRID 586069

Reaction equation

HRID 586069 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1F)[C:5]#[N:6].Cl.[CH:12]12[NH:19][CH:16]([CH2:17][CH2:18]1)[CH2:15][CH2:14][CH2:13]2.C(N(C(C)C)CC)(C)C>CS(C)=O.[Cl-].[Na+].O>[CH:16]12[N:19]([C:9]3[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=3[F:1])[CH:12]([CH2:18][CH2:17]1)[CH2:13][CH2:14][CH2:15]2

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5222728-Azabicyclo[3.2.1]octane hydrochlorideHCID 5872033,4-Difluorobenzonitrile

Product 1

HCID 223376114-(8-Azabicyclo[3.2.1]oct-8-yl)-3-fluorobenzonitrile

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

3,4-Difluorobenzonitrile (1.75 g; 25.1 mmol), 8-aza-bicyclo[3.2.1]octane hydrochloride (2.1 g; 13.8 mmol), and diisopropylethylamine (3.2 g; 25.1 mmol), were combined in DMSO (30 mL) and heated at 120° C. overnight. The mixture was allowed to cool to ambient temperature, poured into brine (75 mL), and extracted with diethyl ether (2×50 mL). The organics were combined, dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was filtered through a pad of silica gel (ethyl acetate as eluent) to provide the title compound. 1H NMR (DMSO-d6) δ 7.69 (dd, 1H), 7.42 (dd, 1H), 7.15 (t, 1H), 4.41 (s, 2H), 1.98 (m, 2H), 1.62-1.86 (m, 5H), 1.41 (m, 3H); MS (ESI) m/z 231, (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionextracted with diethyl ether (2×50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. filtrationThe residue was filtered through a pad of silica gel (ethyl acetate as eluent)

Sources & evidence

ORD record
ord-2f27ceb37fd64d3a84af97a43a74da87
Source dataset
uspto-grants-2005_08
Patent number
US06933311B2

Linked notes

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