Phosphorus oxychloride → HCID 13812935, compound

HRID 1904934Notes

Reaction equation

HRID 1904934 reaction equation
[N:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[NH:17][CH:18]=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH2:2]1[N:1]2[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:17]=[CH:18][C:9]3=[C:10]2[C:5](=[CH:6][CH:7]=[CH:8]3)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 13812934HCID 13812934, compound

Product 1

HCID 13812935HCID 13812935, compoundYield 29.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 32.8 g of N-[2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]formamide in 500 ml of dry toluene was added 99.6 g of phosphorus oxychloride. The initial solution was heated under nitrogen for 5 hours at 75° and thereafter stirred at room temperature overnight. The solvent and excess phosphorus oxychloride were removed at aspirator pressure with mild heating. The residue was washed twice with ether and twice with hexane to remove traces of phosphorus oxychloride. The residue was triturated and heated with 25 ml of ethanol. The ethanol was removed on a rotary evaporator and the resulting material was treated with 1 liter of ethyl acetate and 50 ml of dilute sodium hydroxide solution. The two phases were stirred vigorously until the residue was dissolved (except for some interfacial material). The dark aqueous layer was separated and back-extracted with 250 ml of ethyl acetate. The combined organic extracts were filtered, washed four times with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to leave 25.2 g. A part of this material (20 g) was purified further by chromatography on 500 g of silica gel (column packed in dichloromethane) using dichloromethane as eluant. The appropriate fractions were combined and concentrated to afford 9.1 g of crystalline product. This material was recrystallized from a small volume of toluene to provide 4.9 g, m.p. 118°-120° C.

Workup

  1. customThe solvent and excess phosphorus oxychloride were removed at aspirator pressure with mild heating
  2. washThe residue was washed twice with ether and twice with hexane
  3. customto remove traces of phosphorus oxychloride
  4. customThe residue was triturated
  5. temperatureheated with 25 ml of ethanol
  6. customThe ethanol was removed on a rotary evaporator
  7. additionthe resulting material was treated with 1 liter of ethyl acetate and 50 ml of dilute sodium hydroxide solution
  8. stirringThe two phases were stirred vigorously until the residue
  9. dissolutionwas dissolved (except for some interfacial material)
  10. customThe dark aqueous layer was separated
  11. extractionback-extracted with 250 ml of ethyl acetate
  12. filtrationThe combined organic extracts were filtered
  13. washwashed four times with water
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationconcentrated in vacuo
  16. customto leave 25.2 g
  17. customA part of this material (20 g) was purified further by chromatography on 500 g of silica gel (column packed in dichloromethane)
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-3218c19a9c6f443b976ed3f9e80ebb1d
Source dataset
uspto-grants-1989_06
Patent number
US04840947

Reaction notes

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