Morpholine → 5-(2-Methyl-1-morpholinopropan-2-yl)isoxazol-3-amine

HRID 631626Notes

Reaction equation

HRID 631626 reaction equation
[N+](C1C=CC(S(O[CH2:14][C:15]([C:18]2[O:22][N:21]=[C:20]([NH2:23])[CH:19]=2)([CH3:17])[CH3:16])(=O)=O)=CC=1)([O-])=O.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C1CCN2C(=NCCC2)CC1>C(#N)C>[CH3:16][C:15]([C:18]1[O:22][N:21]=[C:20]([NH2:23])[CH:19]=1)([CH3:17])[CH2:14][N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 866535282-(3-Aminoisoxazol-5-yl)-2-methylpropyl 4-nitrobenzenesulfonate

Product 1

HCID 668764135-(2-Methyl-1-morpholinopropan-2-yl)isoxazol-3-amineYield 59.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

Six equivalent batches of a stirred mixture of 2-(3-aminoisoxazol-5-yl)-2-methylpropyl 4-nitrobenzenesulfonate (50 mg, 0.15 mmol), morpholine (0.016 mL, 0.179 mmol), DBU (0.027 mL, 0.179 mmol) and acetonitrile (0.75 mL) were heated in a microwave reactor at 140° C. for 2.5 h. After cooling to rt, the reactions were combined and concentrated under reduced pressure. The residue was partitioned between chloroform and saturated aqueous sodium carbonate solution. The organic layer was separated and washed with brine. The organic layer was separated and dried over sodium sulfate, filtrated and concentrated under reduced pressure to give the crude product. Purification via silica gel column chromatography (eluting with a gradient of 100% chloroform to 5% methanol in chloroform) afforded 5-(2-methyl-1-morpholinopropan-2-yl)isoxazol-3-amine (20 mg, 10%) as a solid.

Workup

  1. temperatureAfter cooling to rt
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was partitioned between chloroform and saturated aqueous sodium carbonate solution
  4. customThe organic layer was separated
  5. washwashed with brine
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltrated
  9. concentrationconcentrated under reduced pressure
  10. customto give the crude product
  11. customPurification via silica gel column chromatography (
  12. washeluting with a gradient of 100% chloroform to 5% methanol in chloroform)

Sources & evidence

ORD record
ord-24aa1480496845809fb93b09a485efa2
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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