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Phosphorus oxide (P4O10) → 1-Chloromethyl-6-methoxy-3,4-dihydro-isoquinolinium chloride

HRID 1726434
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HRID 1726434 반응식
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[Cl:15][CH2:16][C:17]([NH:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)=O>CCOCC>[Cl-:15].[Cl:15][CH2:16][C:17]1[C:27]2[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=2)[CH2:21][CH2:20][NH+:19]=1
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참가 물질

4

반응물 2

HCID 14812Phosphorus oxide (P4O10)2회HCID 214755Acetamide, 2-chloro-N-(m-methoxyphenethyl)-

생성물 1

HCID 666570771-Chloromethyl-6-methoxy-3,4-dihydro-isoquinolinium chloride

시약·촉매·용매 1

HCID 3283Diethyl Ether용매2회

실험 절차

Two equiv. of P2O5 (12.9 g) was boiled in xylenes (180 mL) as a 0.25 M solution. The crude product from Step 1 above was also first boiled in xylenes (45 mL) to make a 0.5 M solution, and it was then added dropwise via an addition funnel to the P2O5 solution. The mixture was stirred and heated at reflux for 1 h. The reaction was then cooled to RT and the xylenes decanted off at this point. The flask was then placed in an ice bath and stirred while ice, water, EtOAc, and finally 4 M NaOH were added carefully until the pH>12. Reaction was kept <25° C. until pH=12 was reached. The reaction was then extracted with EtOAc (3×). The combined organic extracts were dried over MgSO4 and concentrated to give a dark solution. This was cooled in an ice bath while 400 mL of cold Et2O was added followed by 100 mL of cold HC1/Et2O. A precipitate formed and was filtered away, washing with Et2O. The solid was immediately placed on high vac for 2 h to give the target product as a colored foamy solid. This crude product was directly used in the next step without further purification.

후처리

  1. temperatureheated
  2. temperatureat reflux for 1 h
  3. customthe xylenes decanted off at this point
  4. customThe flask was then placed in an ice bath
  5. stirringstirred while ice, water, EtOAc, and finally 4 M NaOH
  6. additionwere added carefully until the pH>12
  7. customReaction
  8. customwas kept <25° C. until pH=12
  9. extractionThe reaction was then extracted with EtOAc (3×)
  10. dry with materialThe combined organic extracts were dried over MgSO4
  11. concentrationconcentrated
  12. customto give a dark solution
  13. additionwas added
  14. customA precipitate formed
  15. filtrationwas filtered away
  16. washwashing with Et2O

출처 및 근거

ORD 기록
ord-36a31562957c499fa3c16088768acd61
출처 데이터셋
uspto-grants-2009_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07491794B2

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