1-Butanol → HCID 67201776, compound

HRID 547522Notes

Reaction equation

HRID 547522 reaction equation
CC1C=CC(S([O-])(=O)=O)=CC=1.[CH3:12][N+:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([N+:35]([O-])=O)=[CH:31][CH:30]=3)=[O:27])[CH:21]=2)=[CH:15][CH:14]=1.O.[ClH:39].CCCCO>CCO.[Fe]>[Cl-:39].[NH2:35][C:32]1[CH:33]=[CH:34][C:29]([NH:28][C:26]([C:22]2[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=2)[NH:19][C:16]2[CH:15]=[CH:14][N+:13]([CH3:12])=[CH:18][CH:17]=2)=[O:27])=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 962WaterHCID 86621632HCID 86621632, compound

Product 1

HCID 67201776HCID 67201776, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

Compound C5 (1.59 g, 3.06 mmol) was dissolved in ˜6:1 EtOH:H2O (46 mL), Fe dust (885 mg) was added, and the resulting suspension brought to reflux. Two drops of c.HCl were added, and refluxing was continued for 1 h. (until TLC with the top phase of 5:4:1 mixture of n-BuOH:H2O:CH3CO2H showed complete consumption of starting material). The reaction mixture was diluted with EtOH (100 mL) and brought to reflux. The hot reaction mixture was filtered through a pad of Celite, and the top layer of the Celite pad was boiled with more EtOH and filtered (this procedure was repeated three times to ensure complete extraction of product from iron residues). The combined EtOH extracts were evaporated to dryness, and the residue was extracted with hot water, and filtered through a pad of Celite. The filtrate was concentrated to a smaller volume, and then stirred in pre-washed ion-exchange resin (55g). The resulting slurry was loaded onto a column packed with pre-washed ion-exchange resin and eluted with water. Fractions containing product were combined and evaporated to dryness, and the residue was azeotroped several times with EtOH. The residue was dissolved in a small volume of MeOH, methanolic HCl (1.25 M ,1 mL) was added, and the solution stirred for 10 min. The solution was diluted with EtOAc, and the resulting precipitate filtered and then crystallized from MeOH/EtOAc to give C6 (873 mg, 80%); mp (MeOH/EtOAc)>300° C.; 1H NMR [(CD3)2SO] δ10.77 (br s, 1 H, NH), 9.95 (s, 1 H, NH), 8.41 (br d, J=5.5 Hz, 2 H, Py H-2,6), 7.87-7.84 (m, 2 H, H-2,4), 7.61 (t, J=7.8 Hz, 1 H, H-5), 7.49 (br d, J=7.8 Hz, 1 H, H-6), 7.37 (d, J=8.7 Hz, 2 H, H-2′,6′), 7.21 (br d, J=4.6 Hz, 2 H py H-3,5), 6.55 (d, J=8.8 Hz, 2 H, H-3′,5′), 4.93 (s, 2 H, NH2), 3.97 (s, 3 H, N+CH3).

Workup

  1. temperatureto reflux
  2. temperaturerefluxing
  3. customH2O:CH3CO2H showed complete consumption of starting material)
  4. additionThe reaction mixture was diluted with EtOH (100 mL)
  5. temperatureto reflux
  6. filtrationThe hot reaction mixture was filtered through a pad of Celite
  7. filtrationfiltered (this procedure
  8. extractionextraction of product from iron residues)
  9. customThe combined EtOH extracts were evaporated to dryness
  10. extractionthe residue was extracted with hot water
  11. filtrationfiltered through a pad of Celite
  12. concentrationThe filtrate was concentrated to a smaller volume
  13. washeluted with water
  14. additionFractions containing product
  15. customevaporated to dryness
  16. customthe residue was azeotroped several times with EtOH
  17. dissolutionThe residue was dissolved in a small volume of MeOH, methanolic HCl (1.25 M ,1 mL)
  18. additionwas added
  19. stirringthe solution stirred for 10 min
  20. additionThe solution was diluted with EtOAc
  21. filtrationthe resulting precipitate filtered
  22. customcrystallized from MeOH/EtOAc

Sources & evidence

ORD record
ord-6ddd52e33eff4d5a8b2d164953b6c065
Source dataset
uspto-grants-2011_05
Patent number
US07939546B2

Reaction notes

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