Morpholine → HCID 67263924, compound

HRID 1040966Notes

Reaction equation

HRID 1040966 reaction equation
CO[C:3]1[CH:4]=[CH:5][C:6]([N+:14]([O-:16])=[O:15])=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:8]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>>[N+:14]([C:6]1[CH:5]=[CH:4][C:3]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:8][C:7]=1[N:9]1[CH:13]=[CH:12][CH:11]=[N:10]1)([O-:16])=[O:15]

Participants

3

Reactant 2

HCID 8083MorpholineHCID 67264286HCID 67264286, compound

Product 1

HCID 67263924HCID 67263924, compoundYield 9%

Procedure

Under N2 a solution of 1-(5-Methoxy-2-nitro-phenyl)-1H-pyrazole (3.00 g, 13.7 mmol), of Example 611a, in Morpholine (100 mL, 1000 mmol; Acros) was warmed to 120° C. for 100 h. The reaction mixture was concentrated under reduced pressure and the residue partitioned between 10% Na2CO3 and EtOAc. The aqueous phase was washed with a second portion of EtOAc, then the organics were combined, dried over Na2SO4, filtered and concentrated to yield 1.46 g of crude product 4-(4-Nitro-3-pyrazol-1-yl-phenyl)-morpholine (26% by LC). An initial purification by normal phase chromatography eluting with a gradient of 100% CH2Cl2 to 10:1 CH2Cl2:MeOH met with limited success. The purest fractions were concentrated and rerun on another normal phase column eluting with a gradient of 10% EtOAc/Hexane to 65% EtOAc/Hexane. The purest fractions were combined and concentrated under reduced pressure to give 0.48 g of purer material. This material was crystallized from Et2O and the resulting solid was filtered and rinsed with a small amount of Et2O to yield 318 mg (9%) of 4-(4-Nitro-3-pyrazol-1-yl-phenyl)-morpholine, which was carried on without further purification. 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J=9.25 Hz, 1H), 7.76 (s, 1H), 7.65 (d, J=1.95 Hz, 1H), 6.93 (d, J=2.21 Hz, 1H), 6.86 (m, 1H), 6.50 (s, 1H), 3.87 (m, 4H), 3.40 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue partitioned between 10% Na2CO3 and EtOAc
  3. washThe aqueous phase was washed with a second portion of EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield 1.46 g of crude product 4-(4-Nitro-3-pyrazol-1-yl-phenyl)-morpholine (26% by LC)
  8. customAn initial purification by normal phase chromatography
  9. washeluting with a gradient of 100% CH2Cl2 to 10:1 CH2Cl2
  10. concentrationThe purest fractions were concentrated
  11. washeluting with a gradient of 10% EtOAc/Hexane to 65% EtOAc/Hexane
  12. concentrationconcentrated under reduced pressure
  13. customto give 0.48 g of purer material
  14. customThis material was crystallized from Et2O
  15. filtrationthe resulting solid was filtered
  16. washrinsed with a small amount of Et2O

Sources & evidence

ORD record
ord-9fdf7ae5b1394baa964ca91402767522
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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