Dichloromethane → HCID 23441208, compound

HRID 2119336Notes

Reaction equation

HRID 2119336 reaction equation
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:10]=2)[N:5]([CH:19]=[C:20]([C:26]([O:28]CC)=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:4][C:3]1=[O:31].CS(O)(=O)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[OH-].[Na+].C(Cl)Cl>O>[CH3:1][N:2]1[C:11]2[CH:10]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:8]=[C:7]3[C:26](=[O:28])[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][N:5]([C:6]=23)[CH2:4][C:3]1=[O:31]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 23441203HCID 23441203, compoundHCID 86584057Phosphorus Pentoxide-Methanesulfonic Acid

Product 1

HCID 23441208HCID 23441208, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Diethyl 2-{[4-methyl-6-(morpholin-4-ylmethyl)-3-oxo-3,4-dihydroquinoxalin-1(2H)-yl]methylene}malonate (915 g, 2.20 mol) is added to Eaton's reagent (4.05 kg, 7.7 wt % phosphorus pentoxide dimer in methanesulfonic acid). The resulting dark red mixture is heated to 90° C. After 2 h, the reaction is cooled to less than 30° C. and poured into 9 kg of ice. A solution of 50% NaOH (3.9 kg) in water (3.8 liter) is added while maintaining less than 35° C. until the pH is 10. Methylene chloride (4 liter) is added and the phases separated. The aqueous is washed with methylene chloride (3×4 liter) and the combined organics are concentrated in vacuo to 4.5 liter total volume. Acetonitrile (4.5 liter) is added and the mixture concentrated to 4.5 liter total volume. Acetonitrile (1.8 liter) is added and the mixture concentrated to 4.5 liter total volume. The resultant slurry is cooled to 0° C. and the precipitate collected by filtration, washed with 2×1 liter of 0° C. acetonitrile and dried in a vacuum oven at 50° C. overnight to give a white solid (756 g). Physical characteristics: 1H NMR (400 MHz, DMSO-d6) δ1.27, 2.38, 3.36, 3.59, 4.21, 5.08, 7.33, 7.73, 8.48; 13C NMR (DMSO-d6) δ172.2. 164.2, 161.6, 146.8, 135.4, 131.0, 127.3, 126.4, 119.2, 117.3, 111.3, 66.2, 61.9. 59.9, 53.1, 28.6, 14.3.

Workup

  1. temperaturethe reaction is cooled to less than 30° C.
  2. temperaturewhile maintaining less than 35° C. until the pH is 10
  3. customthe phases separated
  4. washThe aqueous is washed with methylene chloride (3×4 liter)
  5. concentrationthe combined organics are concentrated in vacuo to 4.5 liter total volume
  6. additionAcetonitrile (4.5 liter) is added
  7. concentrationthe mixture concentrated to 4.5 liter total volume
  8. additionAcetonitrile (1.8 liter) is added
  9. concentrationthe mixture concentrated to 4.5 liter total volume
  10. temperatureThe resultant slurry is cooled to 0° C.
  11. filtrationthe precipitate collected by filtration
  12. washwashed with 2×1 liter of 0° C. acetonitrile
  13. customdried in a vacuum oven at 50° C. overnight

Sources & evidence

ORD record
ord-d6ecfc3db2e34b47bca6a3886ef7c10f
Source dataset
uspto-grants-2004_02
Patent number
US06686356B2

Reaction notes

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