Sulfuric acid magnesium salt (1:1) → 4H,5H,6H-pyrrolo(1,2-b)pyrazole-2-carbaldehyde

HRID 1178767Notes

Reaction equation

HRID 1178767 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].CON(C)[C:10]([C:12]1[CH:13]=[C:14]2[CH2:19][CH2:18][CH2:17][N:15]2[N:16]=1)=[O:11].S([O-])([O-])(=O)=O.[Na+].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>O1CCCC1.O>[N:16]1[N:15]2[CH2:17][CH2:18][CH2:19][C:14]2=[CH:13][C:12]=1[CH:10]=[O:11]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 24436Sodium SulfateHCID 11356033N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamideHCID 21226445Aluminium lithium hydride

Product 1

HCID 112864914H,5H,6H-pyrrolo(1,2-b)pyrazole-2-carbaldehydeYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
2.5 °C

Procedure

Lithium aluminum hydride (pellets, 2.90 g, 0.0764 mol) is added to a stirred solution of N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide (30.0 g, 0.154 mol) in anhydrous tetrahydrofuran (300 mL) at 0-5° C. and stirred overnight (20 hours) at 0-5° C. under nitrogen. The mixture is then slowly added to a flask containing water (50 ml) and tetrahydrofuran (50 ml) maintained at 5-15° C. Anhydrous sodium sulfate (8.0 g) and anhydrous magnesium sulfate (4.0 g) are added and the mixture is stirred for 0.5 hours. The mixture is filtered, and the filter pad is washed with tetrahydrofuran (100 ml). The filtrate and washings are evaporated under diminished pressure and the residue is stirred for 20 minutes with dichloromethane (150 ml) and 1.5 N hydrochloric acid (40 ml). The phases are separated and water (200 ml) containing dissolved sodium hydrogensulfite (22 g) is added to the organic phase. The mixture is stirred for 20 minutes and the phases are separated. Fresh dichloromethane (150 mL) and 10 N sodium hydroxide (22 mL) are added (with cooling) to the aqueous phase. The mixture is stirred for 20 minutes and the phases are separated. The organic phase is washed with water (100 ml). The dichloromethane extract is evaporated at 20-70° C. to give an oil which crystallizes on cooling to provide 16.1 g (77%) of 5,6-dihydro-4H-pyrrolo-[1,2-b]-pyrazole-2-carbaldehyde as a light yellow, crystalline solid having HPLC-MS purity 99.95% (HPLC conditions as in example 15).

Workup

  1. additionThe mixture is then slowly added to a flask
  2. temperaturemaintained at 5-15° C
  3. stirringthe mixture is stirred for 0.5 hours
  4. filtrationThe mixture is filtered
  5. washthe filter pad is washed with tetrahydrofuran (100 ml)
  6. customThe filtrate and washings are evaporated under diminished pressure
  7. stirringthe residue is stirred for 20 minutes with dichloromethane (150 ml) and 1.5 N hydrochloric acid (40 ml)
  8. customThe phases are separated
  9. additionwater (200 ml) containing
  10. dissolutiondissolved sodium hydrogensulfite (22 g)
  11. additionis added to the organic phase
  12. stirringThe mixture is stirred for 20 minutes
  13. customthe phases are separated
  14. additionFresh dichloromethane (150 mL) and 10 N sodium hydroxide (22 mL) are added
  15. temperature(with cooling) to the aqueous phase
  16. stirringThe mixture is stirred for 20 minutes
  17. customthe phases are separated
  18. washThe organic phase is washed with water (100 ml)
  19. extractionThe dichloromethane extract
  20. customis evaporated at 20-70° C.
  21. customto give an oil which
  22. customcrystallizes
  23. temperatureon cooling

Sources & evidence

ORD record
ord-f9fa2fc61e5a45c2b54a26c0e0093f79
Source dataset
uspto-grants-2007_10
Patent number
US07276611B2

Reaction notes

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