Toluene → 3-Benzylpyrazin-2-amine

HRID 1034590Notes

Reaction equation

HRID 1034590 reaction equation
CN(C)CCN(C)C.[C:9]1([CH3:15])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CCCCCC.[NH2:22][C:23]1[CH:28]=[N:27][CH:26]=[CH:25][N:24]=1>C1COCC1>[NH2:22][C:23]1[C:28]([CH2:15][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:27][CH:26]=[CH:25][N:24]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 8058HexaneHCID 78747Aminopyrazine

Product 1

HCID 27625483-Benzylpyrazin-2-amineYield 37.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of N,N,N′,N′-tetramethylethylendiamine (TMEDA, 15.00 mL, 0.10 mol) in toluene (22.00 mL, 0.21 mol) at 0° C., buthyllitium 1.6M in n-hexane (63.00 mL, 0.10 mol) was added dropwise. Then the mixture was heated at 60° C. and after 30 min was slowly added to a cooled solution of 2-aminopyrazine 11 (2.00 g, 0.02 mol) in anhydrous THF (20 mL). The reaction mixture was stirred at 0° C. for 30 min, poured into ice and extracted with ethyl acetate (3×20 mL). The organic layer was dried over Na2SO4, filtered and the solvent removed under reduced pressure. The crude was purified by flash chromatography (EtOAc, dichloromethane; 65:35) to get 1.38 g (35% yield) of the title compound 12 as a yellow solid (mp 93-96° C.). 1H-NMR (CDCl3): 4.08 (s, 2H), 4.33 (br s, 2H), 7.18-7.35 (m, 5H), 7.91 (m, 2H). MS (ESI): m/z 186 (M+H−).

Workup

  1. additionpoured into ice
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe crude was purified by flash chromatography (EtOAc, dichloromethane; 65:35)

Sources & evidence

ORD record
ord-189d6e6a4c914a26940e27059ab06766
Source dataset
uspto-grants-2013_10
Patent number
US08546147B2

Reaction notes

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