Water → rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylate

HRID 38774

Reaktionsgleichung

Reaktionsgleichung von HRID 38774
[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[OH:8].[H-].[Na+].Cl[C:12]1[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[C:15]([C:22]([O:24][CH3:25])=[O:23])=[CH:14][N:13]=1.O>O1CCCC1.[Cl-].[Na+].O>[CH:4]12[CH2:7][CH:1]([CH2:2][CH2:3]1)[CH2:6][CH:25]2[O:24][C:22]([C:15]1[C:16]([C:18]([F:21])([F:20])[F:19])=[N:17][C:12]([O:8][C@@H:2]2[CH2:3][C@@H:4]3[CH2:7][C@H:1]2[CH2:6][CH2:5]3)=[N:13][CH:14]=1)=[O:23]

Komponenten

7

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 790282-NorbornanolHCID 3696469Methyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate

Produkt 1

HCID 66720285rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylateAusbeute 44,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

To a solution of rac-(1R,2R,4S)-bicyclo[2.2.1]heptan-2-ol (1.12 g) in tetrahydrofuran (10 mL) was added 60% sodium hydride (400 mg) under ice-cooling, and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was further stirred at an external temperature of 60° C. for 30 minutes, and then ice-cooled, and a mixture of methyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate (481 mg) and tetrahydrofuran (2 mL) was added thereto, followed by stirring at room temperature for 3 hours. To the reaction mixture were added water and saturated brine, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=100:0 to 97:3) to obtain a mixture (351 mg) of rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylate and rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1S,2S,4R)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylate as a colorless oily substance.

Aufarbeitung

  1. temperaturecooling
  2. stirringThe reaction mixture was further stirred at an external temperature of 60° C. for 30 minutes
  3. temperatureice-cooled
  4. additionwas added
  5. stirringby stirring at room temperature for 3 hours
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe obtained organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=100:0 to 97:3)

Quellen und Nachweise

ORD-Eintrag
ord-3270fd3fb74749f0a5c99e80ffb37035
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524727B2

Verknüpfte Notizen

Wird geladen…