Sodium hydride → (S)-2,3,10,10a-tetrahydro-1H,5H-pyrrolo[2,1-c]thieno[2,3-f][1,4]oxazepine-5-one

HRID 1662944Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1662944
Cl[C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7](O)=O.C(N1C=CN=C1)(N1C=CN=C1)=[O:11].[NH:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[CH2:27][OH:28].[H-].[Na+]>CN(C)C=O.O>[S:4]1[CH:3]2[CH2:7][N:22]3[CH:26]=[CH:25][CH:24]=[C:23]3[C:27](=[O:11])[O:28][C@H:2]2[CH2:6][CH2:5]1

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 640091L-ProlinolHCID 7012693-Chlorothiophene-2-carboxylic acid

Produkt 1

HCID 67435148(S)-2,3,10,10a-tetrahydro-1H,5H-pyrrolo[2,1-c]thieno[2,3-f][1,4]oxazepine-5-oneAusbeute 11,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 3-chlorothiophene-2-carboxylic acid (0.5 g; 6.325 mmol) in dimethylformamide (5 ml) was added 1,1′-carbonyldiimidazole (1.07 g; 6.64 mmol) and the solution stirred at room temperature for 1 h, followed by the addition of (S)-(+)-2-pyrrolidinemethanol (0.655 ml; 6.64 mmol). The reaction was stirred at room temperature overnight whereupon 60% sodium hydride in mineral oil (0.507 g; 12.7 mmol) was carefully added and the mixture was heated slowly to 150° C. with the progress of the reaction being monitored by thin layer chromatography. The reaction was cautiously diluted with water and extracted with ethyl acetate and the organic layer washed with water then dried (Na2SO4) and evaporated to give the crude product. Purification by flash chromatography eluting with 0-10% (v/v) methanol in dichloromethane followed by crystalisation from ethyl acetate-petroleum ether (40-60) afforded the title compound (0.15 g). M.p.: 167-167.5° C.; EIMS: m/z=222.2 [M+H]+

Aufarbeitung

  1. additionwas carefully added
  2. temperaturethe mixture was heated slowly to 150° C. with the progress of the reaction
  3. extractionextracted with ethyl acetate
  4. washthe organic layer washed with water
  5. dry with materialthen dried (Na2SO4)
  6. customevaporated
  7. customto give the crude product
  8. customPurification by flash chromatography
  9. washeluting with 0-10% (v/v) methanol in dichloromethane
  10. customfollowed by crystalisation from ethyl acetate-petroleum ether (40-60)

Quellen und Nachweise

ORD-Eintrag
ord-bd8607ce5423464dad66cd1be6570922
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08034804B2

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