1-Bromopropane → 6-Butyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 1183575Notes

Reaction equation

HRID 1183575 reaction equation
C(NC(C)C)(C)C.[CH2:8]([Li])[CH2:9][CH2:10][CH3:11].[C:13]([C:15]1[C:16](=[O:22])[NH:17][C:18](C)=[CH:19][CH:20]=1)#[N:14].BrCCC>C1COCC1>[CH2:8]([C:18]1[NH:17][C:16](=[O:22])[C:15]([C:13]#[N:14])=[CH:20][CH:19]=1)[CH2:9][CH2:10][CH3:11]

Participants

6

Reactant 4

HCID 78401-BromopropaneHCID 7912DiisopropylamineHCID 779193-Pyridinecarbonitrile, 1,2-dihydro-6-methyl-2-oxo-HCID 178418339Butyllithium

Product 1

HCID 114238796-Butyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

A solution of diisopropylamine (20.5 mL, 2 eq) in THF (200 mL) was cooled to −5° C. n-Butyllithium (53.5 mL, 2.9 M in hexanes, 2 eq) was added over 10 minutes. The solution was allowed to rise to 0° C., stirred for 0.5 hours, then cooled again to −30° C. 3-Cyano-6-methyl-2(1H)pyridinone (10 g, 75 mmol) was added portionwise, and the mixture was allowed to warm to room temperature and stirred for 2 hours. The solution was then cooled to −50° C., and 1-bromopropane (6.8 mL, 1 eq) was added. The solution was allowed to warm to room temperature, stirred for 1 hour, and then quenched with a saturated ammonium chloride solution. The THF was evaporated and the aqueous phase extracted with DCM (2×100 mL). The organics were washed with saturated aqueous NaCl, dried over Na2SO4, and evaporated to yield intermediate (24a) as an orange solid (10.8 g, 61 mmol), which was used without further purification. MS m/z: [M+H+] calcd for C10H12N2O, 177.2; found 177.0. 1H-NMR (DMSO) 7.87 (1H, d), 6.05 (1H, d), 2.38 (2H, t), 1.41 (2H, m), 1.15 (2H, m), 0.93 (1H, d), 0.73 (3H, t).

Workup

  1. additionwas added over 10 minutes
  2. customto rise to 0° C.
  3. temperatureto warm to room temperature
  4. stirringstirred for 2 hours
  5. temperatureThe solution was then cooled to −50° C.
  6. temperatureto warm to room temperature
  7. stirringstirred for 1 hour
  8. customquenched with a saturated ammonium chloride solution
  9. customThe THF was evaporated
  10. extractionthe aqueous phase extracted with DCM (2×100 mL)
  11. washThe organics were washed with saturated aqueous NaCl
  12. dry with materialdried over Na2SO4
  13. customevaporated

Sources & evidence

ORD record
ord-4deb473f197946d6bf1eaa96abf6bebd
Source dataset
uspto-grants-2014_03
Patent number
US08664254B2

Reaction notes

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