2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → (S)-3-((E)-2-Methyl-pent-2-enoyl)-4-phenyl-oxazolidin-2-one

HRID 132649

반응식

HRID 132649 반응식
[CH3:1]/[C:2](=[CH:6]\[CH2:7][CH3:8])/[C:3]([OH:5])=O.[C:9]1([C@H:15]2[CH2:19][O:18][C:17](=[O:20])[NH:16]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(OC1C=CC2C(=CC=CC=2)N1C(OCC)=O)C.[Cl-].[Li+]>C(OCC)(=O)C>[CH3:1]/[C:2](=[CH:6]\[CH2:7][CH3:8])/[C:3]([N:16]1[C@@H:15]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:19][O:18][C:17]1=[O:20])=[O:5]

참가 물질

6

반응물 4

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 433294Lithium ChlorideHCID 7304242-Oxazolidinone, 4-phenyl-, (4S)-HCID 53659092-Methyl-2-pentenoic acid

생성물 1

HCID 69048246(S)-3-((E)-2-Methyl-pent-2-enoyl)-4-phenyl-oxazolidin-2-one수율 89.2%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
75 °C

실험 절차

A 20 L jacketed reactor was fitted with a reflux condenser and a nitrogen inlet. To the flask was charged 1006 g (8.81 mol) of (E)-2-methyl-2-pentenoic acid, 1250 g (7.661 mol) of (S)-(+)-4-phenyl-oxazolidin-2-one, 2179 g (8.81 mol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), 81 g (1.915 mol) of lithium chloride, and 12.5 L of ethyl acetate (EtOAc). The reaction was heated to 75° C. for 20 hours and then cooled to room temperature. The reaction solution was extracted 3× with 4 L aliquots of 1N HCl and 1× with 4 L of 0.2N NaOH. The 20 L reactor was fitted with a distillation head. The organic layer was distilled to remove, in succession: 6.5 L of EtOAc, after which 8 L of heptane was added back to the reactor; 4 L of EtOAc/heptane, after which 4 L of heptane was added to the reactor; and 4 L of EtOAc/heptane, after which 8 L of heptane was added to the reactor. After an additional 2 L of EtOAc/heptane was removed by distillation, the reaction mixture was cooled to an internal temperature of 40° C., and the reactor contents were charged to a filter and filtered under 5 psig of nitrogen washing with 8 L of heptane. The solids were dried under 5 psig of nitrogen overnight to give 1772 g of the titled compound: 1H-NMR (DMSO) 7.363-7.243 (m, 5H), 6.137-6.096 (m, 1H), 5.434-5.394 (m, 1H), 4.721-4.678 (t, 1H, J=8.578), 4.109-4.069 (m, 1H), 2.119-2.044 (m, 2H), 1.703-1.700 (d, 3H, J=1.364), 0.945-0.907 (t, 3H, J=7.603); Anal Calc'd for C15H17N1O3: C, 69.48; H, 6.61; N, 5.40. Found: C, 68.66; H, 6.60; N, 5.60; MS (Ion Mode: APCI) m/z=260 [M+1]+.

후처리

  1. customwas fitted with a reflux condenser and a nitrogen inlet
  2. temperaturecooled to room temperature
  3. extractionThe reaction solution was extracted 3× with 4 L aliquots of 1N HCl and 1× with 4 L of 0.2N NaOH
  4. customThe 20 L reactor was fitted with a distillation head
  5. distillationThe organic layer was distilled
  6. customto remove, in succession
  7. addition6.5 L of EtOAc, after which 8 L of heptane was added back to the reactor
  8. addition4 L of EtOAc/heptane, after which 4 L of heptane was added to the reactor
  9. additionand 4 L of EtOAc/heptane, after which 8 L of heptane was added to the reactor
  10. customAfter an additional 2 L of EtOAc/heptane was removed by distillation
  11. temperaturethe reaction mixture was cooled to an internal temperature of 40° C.
  12. additionthe reactor contents were charged to
  13. filtrationa filter
  14. filtrationfiltered under 5 psig of nitrogen washing with 8 L of heptane
  15. customThe solids were dried under 5 psig of nitrogen overnight

출처 및 근거

ORD 기록
ord-af956749bf42444299a6d82d8f175ddd
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388023B2

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