Tetrahydrofuran → 3-Cyano-2-pyrrolidinopyridine

HRID 645633Notes

Reaction equation

HRID 645633 reaction equation
F[C:2]1[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O1CCCC1.[CH2:15]([N:17](CC)[CH2:18][CH3:19])[CH3:16].N1CCCC1>O>[N:17]1([C:2]2[N:9]=[CH:8][CH:7]=[CH:6][C:3]=2[C:4]#[N:5])[CH2:18][CH2:19][CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 31268PyrrolidineHCID 27832543-Cyano-2-fluoropyridine

Product 1

HCID 65020993-Cyano-2-pyrrolidinopyridineYield 75%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To an oven-dried, N2-purged, 50-mL flask containing a magnetic stir bar were added 2-fluoronicotinonitrile (1.22 g, 10.0 mmol), anhydrous tetrahydrofuran (5 mL), and triethylamine (3.04 g, 4.19 mL, 30.0 mmol). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Neat pyrrolidine (1.04 g, 1.24 mmol, 15.0 mmol) was added via syringe. The mixture was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature overnight. Water (10 mL) was added and the mixture was transferred to a separatory funnel. The mixture was extracted with dichloromethane (3×10 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to a brown oil. The product was recrystallized from ethyl acetate/hexanes to give 1.29 g (75%) of the title compound as a tan powder. MS (ESI+) m/z 174.0 (M+H)+; 1H NMR (DMSO-d6) δ 1.91-1.95 (m, 4H), 3.63-3.68 (m, 4H), 6.68 (dd, J=7.6, 4.6 Hz, 1H), 7.91 (dd, J=7.6, 1.9 Hz, 1H), 8.31 (dd, J=4.7, 2.0 Hz, 1H).

Workup

  1. customTo an oven-dried, N2-purged
  2. addition50-mL flask containing a magnetic stir bar
  3. customThe flask was sealed with a septum
  4. temperatureto warm to room temperature overnight
  5. customthe mixture was transferred to a separatory funnel
  6. extractionThe mixture was extracted with dichloromethane (3×10 mL)
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporator to a brown oil
  10. customThe product was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-29770414b7574512b9eb46ee213f6983
Source dataset
uspto-grants-2010_04
Patent number
US07704997B1

Reaction notes

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