Citric Acid → 2-(5-(t-Butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol

HRID 380951

Reaktionsgleichung

Reaktionsgleichung von HRID 380951
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([Cl:15])=[N:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.[CH:21]1([C:24]#[C:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH2:23][CH2:22]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CCCCC>[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([C:26]([OH:31])([C:25]#[C:24][CH:21]2[CH2:22][CH2:23]2)[C:27]([F:28])([F:29])[F:30])=[CH:11][C:12]([Cl:15])=[N:13][CH:14]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 311Citric AcidHCID 7330593(6-Chloro-pyridin-3-yl)-carbamic acid tert-butyl esterHCID 106308184-Cyclopropyl-1,1,1-trifluoro-3-butyn-2-oneHCID 178418306HCID 178418306, Verbindung

Produkt 1

HCID 183865642-(5-(t-Butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8003PentaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred, cooled (−50° C.) solution of 643 mg(2.8 mmol) of 5-(t-butoxycarbonylamino)-2-chloropyridine in 8 mL of anhydrous THF was added 4.7 mL(7.9 mmol) of t-BuLi in pentane over 3 min. The solution was stirred an additional 35 min. at −50° C. after which time 1 mL(large excess) of 4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-one. The solution was stirred an additional 20 min., warming to ambient temperature. The reaction was poured into 10% aq. citric acid, and the mixture was extracted with 1:1 ether-ethyl acetate. The organic extract was washed with saturated aq. NaHCO3, then brine, dried (MgSO4), and concentrated under reduced pressure. Chromatography on silica gel(gradient elution with 6:1 then 3:1 hexanes-ethyl acetate) afforded, after removal of solvent, 620 mg(56%) of 2-(5-(t-butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol as an amorphous solid. Mass spec.(NH3—CI): 391((M+H)+, 100%); 291((M+H-t-Boc)+, 49%). 1H NMR(300 MHz, CDCl3) δ 9.08(br. s, 1H); 8.29(br. s, 1H); 7.59(s, 1H); 1.50(s, 9H); 1.37-1.43(m, 1H); 0.81-0.97(m, 4H).

Aufarbeitung

  1. extractionthe mixture was extracted with 1:1 ether-ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with saturated aq. NaHCO3
  4. dry with materialbrine, dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. washChromatography on silica gel(gradient elution with 6:1
  7. custom3:1 hexanes-ethyl acetate) afforded
  8. customafter removal of solvent, 620 mg(56%) of 2-(5-(t-butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol as an amorphous solid

Quellen und Nachweise

ORD-Eintrag
ord-355dfbb0a3314132a6e076fdf3380959
Quelldatensatz
uspto-grants-2001_10
Patentnummer
US06303780B1

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