Dimethylformamide → HCID 86035953, compound

HRID 751348Notes

Reaction equation

HRID 751348 reaction equation
P(Cl)(Cl)([Cl:3])=O.CN(C)[CH:8]=[O:9].[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][C:18]2=O)[CH:12]=1.[OH-].[NH4+]>ClCCl.O.N1C=CC=CC=1>[Cl:3][CH:18]1[CH:19]([CH:8]=[O:9])[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:17]1[C:13]1[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 67372053HCID 67372053, compound

Product 1

HCID 86035953HCID 86035953, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

Phosphorous oxychloride (500 μL, 5.39 mmol) is added slowly to a stirred solution of dimethylformamide (516 μL) in dichloromethane (516 μL) at 0-5° C. After 15 min, a solution of 1-(pyridin-3-yl)-1,3-dihydroindol-2-one (250 mg, 1.2 mmol) and pyridine (258 μL) in dichloromethane (2 mL) is added. The reaction mixture is warmed to room temperature and stirred for 24 hr. The reaction is diluted with water, made basic with ammonium hydroxide, extracted with dichloromethane and the extract is concentrated. The residue is treated with phosphorous oxychloride (5 mL) and heated at reflux for 2 hr. After cooling to room temperature, the excess phosphorous oxychloride is removed and the residue is treated with ice/water, made basic with ammonium hydroxide and extracted with dichloromethane. The combined extract is washed with brine, dried, filtered and concentrated. The residue is purified by chromatography eluting with pentane-30% ethyl acetate. Product containing fractions are combined and concentrated to afford 2-chloro-1-(pyridin-3-yl)-1,3-dihydroindole-3-carboxaldehyde (42 mg, 14% yield) as a yellow solid.

Workup

  1. extractionextracted with dichloromethane
  2. concentrationthe extract is concentrated
  3. additionThe residue is treated with phosphorous oxychloride (5 mL)
  4. temperatureheated
  5. temperatureat reflux for 2 hr
  6. temperatureAfter cooling to room temperature
  7. customthe excess phosphorous oxychloride is removed
  8. additionthe residue is treated with ice/water
  9. extractionextracted with dichloromethane
  10. extractionThe combined extract
  11. washis washed with brine
  12. customdried
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue is purified by chromatography
  16. washeluting with pentane-30% ethyl acetate
  17. additionProduct containing fractions
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-f2fe895e29f14f5c867aa7e378911306
Source dataset
uspto-grants-2008_07
Patent number
US07405300B2

Reaction notes

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