Pyrazine → 2-(2-Methyl-3-{[(oxan-2-yl)oxy]methyl}phenyl)pyrazine

HRID 2295863Notes

Reaction equation

HRID 2295863 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][CH:2]=1.[O:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](N)[C:16]=1[CH3:22].N(OC(C)(C)C)=O>C1(C)C=CC=CC=1>[O:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][N:1]=2)[C:16]=1[CH3:22]

Participants

5

Reactant 3

HCID 9261PyrazineHCID 10906Tert-Butyl nitriteHCID 132459402-Methyl-3-{[(oxan-2-yl)oxy]methyl}aniline

Product 1

HCID 132434252-(2-Methyl-3-{[(oxan-2-yl)oxy]methyl}phenyl)pyrazineYield 1.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred solution of 50.0 g (0.624 mol) of pyrazine and 13.8 g (0.624 mol) of 3-amino-2-methylbenzenemethanol tetrahydropyranyl ether was warmed to 84° C.±6° C. and 9.6 g (0.094 mol) of t-butyl nitrite was added dropwise during 10 minutes. Upon complete addition, the reaction mixture was stirred at 85° C.±6° C. for 0.75 hours, then allowed to cool slowly to ambient temperature. The reaction mixture was dissolved in 100 mL of toluene, and subjected to column chromatography on silica gel, eluting with toluene-methylene chloride (3:1), methylene chloride, and finally ethyl acetate-methylene chloride (4:1). All the fractions were combined and subjected to a second column chromatography on silica gel, eluting with ethyl acetate-methylene chloride (1:19), ethyl acetate-methylene chloride (1:9), and ethyl acetate. The appropriate fractions were combined and concentrated under reduced pressure to give a residual oil. The oil was subjected to distillation under reduced pressure using a Kugelrohr distilling system to give 2.4 g of 2-methyl-3-(pyrazinyl)-benzenemethanol tetrahydropyranyl ether, b.p. 163° C.±3° C./0.04 mm.

Workup

  1. additionUpon complete addition
  2. washeluting with toluene-methylene chloride (3:1), methylene chloride, and finally ethyl acetate-methylene chloride (4:1)
  3. washeluting with ethyl acetate-methylene chloride (1:19), ethyl acetate-methylene chloride (1:9), and ethyl acetate
  4. concentrationconcentrated under reduced pressure
  5. customto give a residual oil
  6. distillationThe oil was subjected to distillation under reduced pressure
  7. distillationdistilling system

Sources & evidence

ORD record
ord-0b2855681bf94f09a260641c8d3beb01
Source dataset
uspto-grants-1984_01
Patent number
US04426524

Reaction notes

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