N,N,N',N'-Tetramethylethylenediamine → 3-Methylpyridin-2-yl(1-methyltetrazol-5-yl)methanone

HRID 1091995Notes

Reaction equation

HRID 1091995 reaction equation
[CH3:1][N:2]1[CH:6]=[N:5][N:4]=[N:3]1.CN(CCN(C)C)C.[Li]CCCC.CN(OC)[C:22]([C:24]1[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][N:25]=1)=[O:23].C([O-])(O)=O.[Na+]>C1COCC1>[CH3:30][C:29]1[C:24]([C:22]([C:6]2[N:2]([CH3:1])[N:3]=[N:4][N:5]=2)=[O:23])=[N:25][CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 1401231H-Tetrazole, 1-methyl-HCID 516892Sodium BicarbonateHCID 11984046N-methoxy-N,3-dimethylpicolinamideHCID 178418339Butyllithium

Product 1

HCID 577923253-Methylpyridin-2-yl(1-methyltetrazol-5-yl)methanoneYield 39.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-methyltetrazole (2.9 g, 34.7 mmol) and TMEDA (10 ml, 66.2 mmol) in THF (100 ml) cooled at −78° C. is added dropwise 2.5 M nBuLi in hexanes (13.9 ml, 34.7 mmol) with vigorous stirring and maintaining the reaction temperature below −65° C. On complete addition, the mixture is is stirred 20 minutes before adding dropwise a solution of N-methyl-N-methoxy-(3-methylpyridin-2-yl)carboxamide (6.3 g, 34.7 mmol) in THF. On complete addition, the mixture is stirred for six hours at −78° C. before adding slowly a half-diluted saturated aqueous NaHCO3 solution (300 ml). The mixture is extracted with ethyl acetate (500 ml). After separation, the organic layer is dried (MgSO4), filtered and concentrated. Silica-gel chromatography of the residue affords 2.8 g of (3-methylpyridin-2-yl)-(1-methyltetrazol-5-yl)methanone [yield 39.7%; 1H-NMR (DMSO-d6) δppm: 2.6 (s, 3H), 4.17 (s, 3H), 7.65 (dd, 1H), 7.95 (d, 1H), 8.56 (d, 1H)].

Workup

  1. temperaturemaintaining the reaction temperature below −65° C
  2. additionOn complete addition
  3. stirringthe mixture is is stirred 20 minutes
  4. additionOn complete addition
  5. stirringthe mixture is stirred for six hours at −78° C.
  6. extractionThe mixture is extracted with ethyl acetate (500 ml)
  7. customAfter separation
  8. dry with materialthe organic layer is dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ade1482006344911a807202acf08e3fe
Source dataset
uspto-grants-2012_03
Patent number
US08129415B2

Reaction notes

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