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

HRID 469748노트

반응식

HRID 469748 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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+.

후처리

  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

출처 및 근거

ORD 기록
ord-c0ed6ac0eb3c4d4da3a4a587317b5162
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629157B2

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