Dimethylformamide → Ethyl 2-methylquinoline-3-carboxylate

HRID 1650883Notes

Reaction equation

HRID 1650883 reaction equation
[CH3:1]N(C)C=O.O=P(Cl)(Cl)Cl.[NH:11](/[C:18](/[CH3:25])=[CH:19]\[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(Cl)Cl.C(OCC)(=O)C>[CH3:25][C:18]1[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:1][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 5399016HCID 5399016, compound

Product 1

HCID 647634Ethyl 2-methylquinoline-3-carboxylateYield 58.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 140 g of dimethylformamide (1.92 mole ) in 500 mL of methylene chloride is mechanically stirred under a condenser/scrubber in an ice bath while 295 g of POCl3 (1.92 mol) is added dropwise over a 40 minute period. The reaction is stirred for a further 3 hour period, during which time the bath temperature is allowed to warm to room temperature. The reaction is then diluted with 2 L of methylene chloride, cooled in an ice bath, and treated dropwise with 394 g of ethyl β-anilinocrotonate (1.92 mol) over a 1 hour period. After stirring at room temperature for 26 hours, the reaction is heated at reflux temperature for 48 hours, cooled in an ice bath, quenched with 500 mL ice water, and treated portionwise with concentrated NH4OH to pH 6. The phases are separated and the organic phase is concentrated in vacuo to give a solid residue which is redissolved in 1.5 L ethyl acetate, filtered, and the filtrate saturated with gaseous hydrogen chloride. The resultant solid precipitate is filtered off, washed thoroughly with ethyl acetate, dissolved in water and basified with concentrated NH4OH. The basic aqueous mixture is extracted with 1:1 hexanes-ethyl acetate; the organic phase is concentrated in vacuo to afford 240 g of the title product, mp 70°-72° C.

Workup

  1. additionis added dropwise over a 40 minute period
  2. temperaturecooled in an ice bath
  3. stirringAfter stirring at room temperature for 26 hours
  4. temperaturethe reaction is heated
  5. temperatureat reflux temperature for 48 hours
  6. temperaturecooled in an ice bath
  7. customquenched with 500 mL ice water
  8. additiontreated portionwise with concentrated NH4OH to pH 6
  9. customThe phases are separated
  10. concentrationthe organic phase is concentrated in vacuo
  11. customto give a solid residue which
  12. filtrationfiltered
  13. filtrationThe resultant solid precipitate is filtered off
  14. washwashed thoroughly with ethyl acetate
  15. dissolutiondissolved in water and basified with concentrated NH4OH
  16. extractionThe basic aqueous mixture is extracted with 1:1 hexanes-ethyl acetate
  17. concentrationthe organic phase is concentrated in vacuo

Sources & evidence

ORD record
ord-30b2b877cb6c4d6e8c43c4db619a893e
Source dataset
uspto-grants-1990_05
Patent number
US04925944

Reaction notes

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