4-Methylmorpholine → rac-{2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidin-5-yl}methanol

HRID 38769Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 38769
[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]([C:19](O)=[O:20])=[CH:11][N:10]=1.CN1CCOCC1.ClC(OCC(C)C)=O>COCCOC>[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[C:12]([CH2:19][OH:20])=[CH:11][N:10]=1

Komponenten

5

Edukt 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 66720245rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid

Produkt 1

HCID 66720204rac-{2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidin-5-yl}methanolAusbeute 55,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

A mixture of rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid (2.0 g), 4-methyl morpholine (1.1 mL) and 1,2-dimethoxyethane (40 mL) was cooled to −10° C., isobutyl chloroformate (1.1 mL) was added thereto, and the mixture was stirred at the same temperature for 1 hour. The insoluble materials in the reaction mixture were filtered and washed with 1,2-dimethoxyethane. The filtrate was cooled to −60° C. and a solution of sodium borohydride (377 mg) in water (4.0 mL) was added thereto, followed by stirring as it is for 1 hour. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=10:90 to 20:80) to obtain rac-{2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidin-5-yl}methanol (1.05 g) as a colorless oily substance.

Aufarbeitung

  1. filtrationThe insoluble materials in the reaction mixture were filtered
  2. washwashed with 1,2-dimethoxyethane
  3. temperatureThe filtrate was cooled to −60° C.
  4. additiona solution of sodium borohydride (377 mg) in water (4.0 mL) was added
  5. stirringby stirring as it
  6. waitis for 1 hour
  7. additionTo the reaction mixture was added water
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe organic layer was washed with water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=10:90 to 20:80)

Quellen und Nachweise

ORD-Eintrag
ord-b597ceaf3b364db28b9e915f6e5f73be
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524727B2

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