Phosphorus oxide (P4O10) → 1-(2-Methylphenyl)-3-(4-pyridyl)isoquinoline

HRID 464320Notes

Reaction equation

HRID 464320 reaction equation
[C:1]1([CH2:7][CH:8]([NH:15][C:16](=O)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH3:23])[C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C1C2C(=CC=CC=2)CCC1>[CH3:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:16]1[C:6]2[C:1](=[CH:2][CH:3]=[CH:4][CH:5]=2)[CH:7]=[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[N:15]=1

Participants

4

Reactant 2

HCID 14812Phosphorus oxide (P4O10)2×HCID 13319930N-[2-phenyl-1-(4-pyridyl)ethyl]-2-methylbenzamide

Product 1

HCID 133199311-(2-Methylphenyl)-3-(4-pyridyl)isoquinolineYield 72.1%

Reagents, catalysts & solvents 1

HCID 8404TetralinSolvent

Conditions

Temperature
230 °C

Procedure

37 g of N-[2-phenyl-1-(4-pyridyl)ethyl]-2-methylbenzamide in 800 ml of tetralin are heated with 240 g of phosphorus pentoxide and 60 g of Celite filtration aid, to improve distribution, at 180°-200° C. for 5 hours. After cooling to 120°-140° C., a further 120 g of phosphorus pentoxide are added and the mixture is heated at 230° C. (reflux) for 16 hours. After cooling, the tetralin is decanted off and the residue is washed several times with toluene. The washed residue is suspended in toluene and water is slowly added with stirring. The aqueous phase is separated off and made highly alkaline with potassium hydroxide. The product is extracted with toluene and, after distilling out the toluene, is chromatographed on silica gel using chloroform/ethyl acetate (8:2). 25 g of oily base are isolated, which provides a hydrochloride of melting point 255°-259° C. with ethanolic hydrochloric acid.

Workup

  1. temperatureAfter cooling to 120°-140° C.
  2. temperature(reflux) for 16 hours
  3. temperatureAfter cooling
  4. customthe tetralin is decanted off
  5. washthe residue is washed several times with toluene
  6. additionwater is slowly added
  7. customThe aqueous phase is separated off
  8. extractionThe product is extracted with toluene
  9. distillationafter distilling out the toluene
  10. customis chromatographed on silica gel

Sources & evidence

ORD record
ord-7d9949f61041419ba6c44b1fd328cc10
Source dataset
uspto-grants-1985_10
Patent number
US04547508

Reaction notes

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