Hydrochloric Acid → HCID 71090134, compound

HRID 716815Notes

Reaction equation

HRID 716815 reaction equation
[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([OH:11])[CH:9]=2)[CH2:4][O:3]1.Cl[C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][N:15]=1.CN(C=O)C.Cl>[Fe]>[CH3:1][C:2]1([CH3:12])[C:10]2[CH:9]=[C:8]([O:11][C:14]3[N:15]=[CH:16][C:17]([NH2:20])=[CH:18][CH:19]=3)[CH:7]=[CH:6][C:5]=2[CH2:4][O:3]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 783082-Chloro-5-nitropyridineHCID 57076460HCID 57076460, compound2×

Product 1

HCID 71090134HCID 71090134, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Conditions

Temperature
80 °C

Procedure

To a solution of 3,3-dimethyl-1H-isobenzofuran-5-ol (Intermediate 18, 30 mg, 0.18 mmol) and 2-chloro-5-nitro-pyridine (27.5 mg, 0.1736 mmol) in DMF (1 mL) dipotassium carbonate (37.8 mg, 0.2741 mmol) was added and the reaction mixture was stirred for 1.5 hours at 80° C. After cooling the reaction was quenched with water (1 ml), diluted with brine (5 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was dissolved in ethanol (3 mL)/water (1 mL). Iron (61.2 mg, 1.1 mmol) and an aqueous 6M solution of hydrogen chloride (0.03 ml, 0.18 mmol) were added and the reaction mixture was stirred for 4 hours at 50° C. The catalyst was filtered off and the resulting solution was diluted with a saturated solution of NaHCO3 (15 ml) and extracted with ethyl acetate (2×20 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 10 g as column and cyclohexane/ethyl acetate from 80:20 to 30:70 as eluent affording the title compound (20 mg) as colourless oil.

Workup

  1. temperatureAfter cooling the reaction
  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 (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionthe residue was dissolved in ethanol (3 mL)/water (1 mL)
  9. stirringthe reaction mixture was stirred for 4 hours at 50° C
  10. filtrationThe catalyst was filtered off
  11. additionthe resulting solution was diluted with a saturated solution of NaHCO3 (15 ml)
  12. extractionextracted with ethyl acetate (2×20 ml)
  13. dry with materialThe organic layer was dried (Na2SO4)
  14. filtrationfiltered
  15. customevaporated
  16. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 10 g as column and cyclohexane/ethyl acetate from 80:20 to 30:70 as eluent

Sources & evidence

ORD record
ord-a6e9d2d7e4934a9694b69b772a40e793
Source dataset
uspto-grants-2015_11
Patent number
US09193704B2

Reaction notes

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