5-Bromo-2,4-bis(1,1-dimethylethoxy)pyrimidine → (+/-)-5-(9,10-Dihydro-4-hydroxy-2,7-dimethyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-2,4(1H,3H)-pyrimidinedione

HRID 324427

Reaktionsgleichung

Reaktionsgleichung von HRID 324427
Br[C:2]1[C:3]([O:13]C(C)(C)C)=[N:4][C:5]([O:8]C(C)(C)C)=[N:6][CH:7]=1.C([Li])CCC.[CH3:23][C:24]1[O:25][C:26]2[CH2:33][CH2:32][C:31]3[CH:34]=[C:35]([CH3:38])[CH:36]=[CH:37][C:30]=3[C:29](=[O:39])[C:27]=2[N:28]=1>O1CCCC1.C(O)(=O)C>[OH:39][C:29]1([C:2]2[C:3](=[O:13])[NH:4][C:5](=[O:8])[NH:6][CH:7]=2)[C:27]2[N:28]=[C:24]([CH3:23])[O:25][C:26]=2[CH2:33][CH2:32][C:31]2[CH:34]=[C:35]([CH3:38])[CH:36]=[CH:37][C:30]1=2

Komponenten

6

Edukt 3

HCID 8188515-Bromo-2,4-bis(1,1-dimethylethoxy)pyrimidineHCID 220036339,10-Dihydro-2,7-dimethyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-oneHCID 178418339Butyllithium

Produkt 1

HCID 70113848(+/-)-5-(9,10-Dihydro-4-hydroxy-2,7-dimethyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-2,4(1H,3H)-pyrimidinedione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of the product from example 1 step (vi) (9 g) in dry tetrahydrafuran (100 ml) under nitrogen at −78° C. was added n-butyllithium (2.5M, 14.3 ml) dropwise over 1 min. After 30 min a warm solution of the product from step (v) (6.73 g) in tetrahydrofuran (350 ml) was added rapidly via cannula. After further stirring for 1 h the cooling bath was removed and the mixture allowed to stir at room temperature for 30 min. The reaction mixture was quenched with saturated brine and extracted with ethyl acetate (×2). The combined organic extracts were dried over magnesium sulphate and solvent removed under reduced pressure to leave a pale yellow foam. This was dissolved in acetic acid (100 ml) and stired at room temperature for 16 h. The solvent was evaporated under reduced pressure and the residue azeotroped with toluene (×2) to remove last traces of acetic acid. The remaining residue was triturated with diethyl ether/isohexane mixtures and filtered to give the subtitle product as a beige solid.

Aufarbeitung

  1. customwas removed
  2. stirringto stir at room temperature for 30 min
  3. customThe reaction mixture was quenched with saturated brine
  4. extractionextracted with ethyl acetate (×2)
  5. dry with materialThe combined organic extracts were dried over magnesium sulphate and solvent
  6. customremoved under reduced pressure
  7. customto leave a pale yellow foam
  8. waitstired at room temperature for 16 h
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue azeotroped with toluene (×2)
  11. customto remove last traces of acetic acid
  12. customThe remaining residue was triturated with diethyl ether/isohexane mixtures
  13. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-65e682c4b4124404abedce50eb29b36c
Quelldatensatz
uspto-grants-2001_04
Patentnummer
US06218376B1

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