Citric Acid → tert-butyl 2-cyano-2-(1-methyl-1H-pyrazol-5-yl)acetate

HRID 931131Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 931131
[C:1]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].CC(C)([O-])C.[K+].I[C:18]1[N:22]([CH3:23])[N:21]=[CH:20][CH:19]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1.C(OCC)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([CH:3]([C:18]1[N:22]([CH3:23])[N:21]=[CH:20][CH:19]=1)[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2]

Komponenten

8

Edukt 4

HCID 311Citric AcidHCID 70693tert-Butyl cyanoacetateHCID 133340655-Iodo-1-methyl-1H-pyrazoleHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 117966348tert-butyl 2-cyano-2-(1-methyl-1H-pyrazol-5-yl)acetateAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a solution of tert-butyl cyanoacetate (340 μL, 2.40 mmol) in 1,4-dioxane (5 mL) was added potassium t-butoxide (1M in tetrahydrofuran, 5 mL, 5.0 mmol) at room temperature. After 10 min, a solution of 5-iodo-1-methyl-1H-pyrazole (500 mg, 2.40 mmol) in 1,4-dioxane (5 mL) and tetrakis(triphenylphosphine)palladium(0) (75 mg, 0.065 mmol) were added. The reaction mixture was stirred for 16 h at 70° C. The mixture was cooled and then was diluted with diethyl ether (50 mL) and a 10% aqueous solution of citric acid. The organic layer was separated and the aqueous layer was extracted with diethyl ether (2×10 mL). The combined organics were washed with brine (15 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Gradient: 30% to 40% ethyl acetate in heptane) to afford tert-butyl 2-cyano-2-(1-methyl-1H-pyrazol-5-yl)acetate (132.8 mg) as a pale brown oil. MS (ES+) (M+H) 222.0, LCMS retention time: 2.74 min (Method L); 1H NMR (500 MHz, CDCl3) δ 1.50 (s, 9H), 3.93 (s, 3H), 4.80 (s, 1H), 6.39 (d, 1H), 7.48 (d 1H).

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with diethyl ether (2×10 mL)
  4. washThe combined organics were washed with brine (15 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (Gradient: 30% to 40% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-dd2cefdf640247808bca688a6178b7f7
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09296745B2

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