Dimethylformamide → HCID 67960657, compound

HRID 527640Notes

Reaction equation

HRID 527640 reaction equation
[CH2:1]([C:3]1([CH2:13][CH3:14])[C:11]2[C:10]([OH:12])=[CH:9][CH:8]=[CH:7][C:6]=2[CH2:5][O:4]1)[CH3:2].CN(C=O)C.Cl[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][N:22]=1.[Cl-].[NH4+]>O1CCCC1.O.[Fe]>[CH2:13]([C:3]1([CH2:1][CH3:2])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][C:21]2[N:22]=[CH:23][C:24]([NH2:27])=[CH:25][CH:26]=2)[CH2:5][O:4]1)[CH3:14]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 783082-Chloro-5-nitropyridineHCID 67960171HCID 67960171, compound2×

Product 1

HCID 67960657HCID 67960657, compoundYield 58.6%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3,3-diethyl-1H-isobenzofuran-4-ol (Intermediate 179, 0.03 g, 0.15 mmol) in dry DMF (3 ml) potassium carbonate (0.08 g, 0.6 mmol) and then 2-Chloro-5-Nitropyridine (0.026 g, 0.17 mmoli) were added and the reaction mixture was stirred for 2 hours at 80° C. After cooling the reaction mixture was quenched with water (1 ml), diluted with brine (5 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was dried over sodium sulfate, filtered and evaporated. The residue was dissolved in tetrahydrofuran (5 ml)/water (2.5 ml), iron (0.04 g, 0.75 mmol) and then ammonium chloride (0.4 g, 0.75 mmol) were added and the reaction mixture was stirred overnight at room temperature. The catalyst was filtered off and the residue was diluted with an aqueous saturated solution of NaHCO3 (5 ml) and extracted with ethyl acetate (3×10 ml). The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents affording the title compound (0.025 g) as a light yellow solid.

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customwas quenched with water (1 ml)
  3. additiondiluted with brine (5 ml)
  4. extractionextracted with ethyl acetate (2×10 ml)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. stirringthe reaction mixture was stirred overnight at room temperature
  9. filtrationThe catalyst was filtered off
  10. additionthe residue was diluted with an aqueous saturated solution of NaHCO3 (5 ml)
  11. extractionextracted with ethyl acetate (3×10 ml)
  12. dry with materialThe organic layer was dried over sodium sulphate
  13. filtrationfiltered
  14. customevaporated
  15. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents

Sources & evidence

ORD record
ord-432a5daa648843e8946c857efedc927c
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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