Cyclopropanecarboxaldehyde → [7-N-(tert-Butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazin-8-yl](cyclopropyl)methanol

HRID 133067Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 133067
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])(CC)C.[CH:26]1([CH:29]=[O:30])[CH2:28][CH2:27]1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:18])([F:19])[F:20])[N:16]=[C:10]2[CH:9]1[CH:29]([CH:26]1[CH2:28][CH2:27]1)[OH:30])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

5

Edukt 3

HCID 123114CyclopropanecarboxaldehydeHCID 53393358tert-Butyl 2-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazine-7(8H)-carboxylateHCID 178418400CID 53628100

Produkt 1

HCID 69364591[7-N-(tert-Butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazin-8-yl](cyclopropyl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 1.86 g (6.38 mmol) of 7-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine (Ex. 2, Step A) in 20 mL of toluene at −78° C. was added 5.88 mL (7.65 mmol, 1.3 M solution in cyclohexane) of sec-butyllithium. The reaction mixture was stirred at −78° C. for 20 min, then 0.524 mL (7.01 mmol) of cyclopropanecarboxaldehyde was added dropwise. The reaction mixture was stirred at −78° C. for 10 min. The −78° C. bath was removed and the mixture was allowed to stir at ambient temperature for 1 h. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution and extracted with three portions of ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate, and concentrated to give 2.24 g of crude material. Purification by flash chromatography (silica gel, 7 to 10% ethyl acetate/hexane) gave the title compound as a mixture of 4 diastereomers. LC/MS 363 (M+1).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at −78° C. for 10 min
  2. customThe −78° C. bath was removed
  3. stirringto stir at ambient temperature for 1 h
  4. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution
  5. extractionextracted with three portions of ethyl acetate
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customto give 2.24 g of crude material
  10. customPurification by flash chromatography (silica gel, 7 to 10% ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-e2c046329a6c4c3aaf87194b3707306f
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07390809B2

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