Dichloromethane → HCID 86716065, compound

HRID 627474Notes

Reaction equation

HRID 627474 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:9].[C:10]1([CH:16]([C:20](O)=O)C(O)=O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O=P(Cl)(Cl)[Cl:25].[Al].[NH4+].[OH-].[CH2:31]([Cl:33])Cl>>[Br:1][C:2]1[CH:8]=[C:7]2[C:5](=[CH:4][C:3]=1[F:9])[N:6]=[C:20]([Cl:25])[C:16]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[C:31]2[Cl:33]

Participants

7

Reactant 6

HCID 6344DichloromethaneHCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 75791Phenylmalonic acidHCID 8218484-Bromo-3-fluoroanilineHCID 5359268Aluminum

Product 1

HCID 86716065HCID 86716065, compound

Procedure

A mixture of 4-bromo-3-fluoroaniline (6.54 g, 34.4 mmol), 2-phenylmalonic acid (7.44 g, 41.3 mmol), and POCl3 (32.0 mL, 344 mmol) was stirred at reflux (130° C. aluminum block temperature) for 3 hours. The dark solution was then allowed to cool to room temperature and diluted with DCM (70 mL). This was treated with 100 mL ice and stirred on an ice bath for ˜5 min, and was then treated with 15 M NH4OH dropwise (6 mL) and removed from the ice bath. Stirring at room temperature caused the reaction to warm to a gentle reflux (42° C.), and the reaction was chilled on an ice bath intermittently. After ˜10 min stirring at room temperature the exotherm moderated, the aqueous layer was extracted with DCM (30 mL), and the combined dark clear organic layers were concentrated to provide a brown solid. This was dry load flash chromatographed with a 20% DCM/heptane to 100% DCM gradient to afford a ˜2:1 mol ratio of the title compound and the 5-fluoro regioisomer as a light yellow solid. A portion of this was dry load flash chromatographed with a 20% toluene/heptane to 100% toluene gradient to provide the title compound eluting at 60-70% toluene/heptane.

Workup

  1. stirringstirred on an ice bath for ˜5 min
  2. customremoved from the ice bath
  3. stirringStirring at room temperature
  4. customthe reaction
  5. temperatureto warm to
  6. temperaturea gentle reflux (42° C.)
  7. temperaturethe reaction was chilled on an ice bath intermittently
  8. stirringAfter ˜10 min stirring at room temperature the exotherm moderated, the aqueous layer
  9. extractionwas extracted with DCM (30 mL)
  10. concentrationthe combined dark clear organic layers were concentrated
  11. customto provide a brown solid
  12. customThis was dry load flash
  13. customchromatographed with a 20% DCM/heptane to 100% DCM gradient
  14. customto afford a ˜2

Sources & evidence

ORD record
ord-47f541b457ea41feb12268b76bf4b0cb
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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