L-Pyroglutamic Acid → (S)-5-oxo-pyrrolidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

HRID 469748Notes

Reaction equation

HRID 469748 reaction equation
[O:1]=[C:2]1[NH:6][C@H:5]([C:7]([OH:9])=O)[CH2:4][CH2:3]1.S(Cl)(Cl)=O.[C:14]([C:18]1[CH:22]=[C:21]([NH2:23])[O:20][N:19]=1)([CH3:17])([CH3:16])[CH3:15].C(NC(C)C)(C)C>O1CCCC1.ClCCl>[C:14]([C:18]1[CH:22]=[C:21]([NH:23][C:7]([C@@H:5]2[CH2:4][CH2:3][C:2](=[O:1])[NH:6]2)=[O:9])[O:20][N:19]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 7405L-Pyroglutamic AcidHCID 7912DiisopropylamineHCID 24386Thionyl ChlorideHCID 20956943-Tert-butyl-1,2-oxazol-5-amine

Product 1

HCID 67454707(S)-5-oxo-pyrrolidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amideYield 32.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To solution of the (S)-5-oxo-pyrrolidine-2-carboxylic acid (6 g, 46.47 mmol) in tetrahydrofuran (50 mL) is added thionyl chloride (6.75 ml, 92.94 mmol) and stirred at room temperature for 2-3 hours. The solvent is removed under reduced pressure and the residue is dissolved in tetrahydrofuran (20 mL) and added dropwise to a solution of 3-tert-butyl-isoxazol-5-ylamine (6.514 g, 46.47 mmol) and diisopropylamine (24.28 ml, 139.41 mmol) in tetrahydrofuran (50 mL) at room temperature. The reaction is stirred overnight at room temperature then diluted with dichloromethane and washed sequentially with water and saturated brine solution. The organics are dried over sodium sulfate, filtered and solvents removed under vacuum. The crude residue is purified by flash column chromatography eluting with 5-10% methanol/dichloromethane. The product rich fractions are pooled and evaporated to afford 3.02 g title compound, 32.7% yield. ESI m/z 252=MH+.

Workup

  1. customThe solvent is removed under reduced pressure
  2. dissolutionthe residue is dissolved in tetrahydrofuran (20 mL)
  3. stirringThe reaction is stirred overnight at room temperature
  4. washwashed sequentially with water and saturated brine solution
  5. dry with materialThe organics are dried over sodium sulfate
  6. filtrationfiltered
  7. customsolvents removed under vacuum
  8. customThe crude residue is purified by flash column chromatography
  9. washeluting with 5-10% methanol/dichloromethane
  10. customevaporated

Sources & evidence

ORD record
ord-c0ed6ac0eb3c4d4da3a4a587317b5162
Source dataset
uspto-grants-2014_01
Patent number
US08629157B2

Reaction notes

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