Ammonium Chloride → Ethyl 5-Cyano-6-methylnicotinate

HRID 1397329Notes

Reaction equation

HRID 1397329 reaction equation
[Cl-].[NH4+].Cl[C:4]1[N:14]=[C:13]([CH3:15])[C:12]([C:16]#[N:17])=[CH:11][C:5]=1[C:6]([O:8][CH2:9][CH3:10])=[O:7]>O1CCOCC1.C1COCC1.CN(C=O)C.CCOC(C)=O.[Zn]>[C:16]([C:12]1[C:13]([CH3:15])=[N:14][CH:4]=[C:5]([CH:11]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:17]

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 2758816Ethyl 2-chloro-5-cyano-6-methylnicotinate

Product 1

HCID 13600369Ethyl 5-Cyano-6-methylnicotinateYield 27.5%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 8857Ethyl AcetateSolventHCID 86677592HCID 86677592, compoundSolvent

Procedure

Ammonium chloride (3.58 g, 66.7 mmol in 10 mL water) was added to a solution of ethyl 2-chloro-5-cyano-6-methylnicotinate (1.0 g, 4.4 mmol) in dioxane-THF-DMF (50 mL, 3:1:1), followed by zinc powder (2.3 g, 35.6 mmol) portionwise at room temperature. The reaction mixture was allowed to stir at room temperature for 3 h, diluted with EtOAc, and filtered through a pad of Celite. The clear filtrate of organic layer was washed with H2O and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 10-15% EtOAc in petroleum ether) to afford ethyl 5-cyano-6-methylnicotinate (230 mg, yield 27%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 9.25 (d, J=2.0 Hz, 1H), 8.49 (d, J=2.0 Hz, 1H), 7.27 (s, 1H), 4.47-4.42 (q, J=7.2 Hz, 2H), 2.86 (s, 3H), 1.45-1.41 (t, J=7.0 Hz, 3H). MS (ESI) m/z: Calculated for C10H10N2O2: 190.07. found: 191.2 (M+H)+.

Workup

  1. filtrationfiltered through a pad of Celite
  2. washThe clear filtrate of organic layer was washed with H2O and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 10-15% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-c6fa8a38f81b44e4a5878d70f9dd4b81
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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