Acetic Acid → 2-Diethoxyphosphoryl-1-[1-(4-methyl-2-pyridyl)-4-piperidyl]ethanone

HRID 1775352

반응식

HRID 1775352 반응식
[CH3:1][P:2](=[O:9])([O:6][CH2:7][CH3:8])[O:3][CH2:4][CH3:5].C([Li])CCC.[CH3:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([N:22]2[CH2:27][CH2:26][CH:25]([C:28](OCC)=[O:29])[CH2:24][CH2:23]2)[CH:17]=1.C(O)(=O)C>C1COCC1>[CH2:4]([O:3][P:2]([CH2:1][C:28]([CH:25]1[CH2:26][CH2:27][N:22]([C:18]2[CH:17]=[C:16]([CH3:15])[CH:21]=[CH:20][N:19]=2)[CH2:23][CH2:24]1)=[O:29])([O:6][CH2:7][CH3:8])=[O:9])[CH3:5]

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 12685Diethyl methylphosphonateHCID 62007359Ethyl 1-(4-methyl-2-pyridyl)piperidine-4-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 898258172-Diethoxyphosphoryl-1-[1-(4-methyl-2-pyridyl)-4-piperidyl]ethanone

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

Diethyl methylphosphonate (1.27 g, 8.36 mmol) was dissolved in anhydrous THF (7 ml), the solution was purged with argon and cooled to −78° C. n-Butyllithium (2M in hexane, 2.67 ml, 5.34 mmol) was added at such a rate that the temperature remained below −65° C. After addition was complete, stirring was continued for 20 minutes, then a solution of ethyl 1-(4-methyl-2-pyridyl)piperidine-4-carboxylate (626 mg, 2.52 mmol) in anhydrous THF (1 ml) was added dropwise so that the temperature remained below −70° C. Stirring was continued overnight while the temperature was allowed to reach room temperature. The mixture was neutralized with glacial acetic acid, concentrated under reduced pressure, water was added and the mixture was extracted with DCM (3×). The combined organic phases were dried (sodium sulfate), and concentrated under reduced pressure to give a brown oil that was used directly in the next step MS (multi-mode) m/z=355.1 [M+1]+.

후처리

  1. customthe solution was purged with argon
  2. additionwas added at such a rate that the temperature
  3. customremained below −65° C
  4. additionAfter addition
  5. customremained below −70° C
  6. stirringStirring
  7. waitwas continued overnight while the temperature
  8. customto reach room temperature
  9. concentrationconcentrated under reduced pressure, water
  10. additionwas added
  11. extractionthe mixture was extracted with DCM (3×)
  12. dry with materialThe combined organic phases were dried (sodium sulfate)
  13. concentrationconcentrated under reduced pressure
  14. customto give a brown oil that

출처 및 근거

ORD 기록
ord-f37bccb58b9c4b7282698af3d7970317
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09260441B2

연결된 노트

불러오는 중…