Toluene → tert-butyl (3R)-4-(5-fluoro-6-methylpyridin-2-yl)-3-methylpiperazine-1-carboxylate

HRID 69127Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69127
Br[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][CH:3]=1.[CH3:10][C@H:11]1[NH:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.O>[F:9][C:5]1[CH:4]=[CH:3][C:2]([N:16]2[CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][C@H:11]2[CH3:10])=[N:7][C:6]=1[CH3:8]

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 2756811(R)-1-Boc-3-methylpiperazineHCID 27831806-Bromo-3-fluoro-2-methylpyridineHCID 23676156Sodium t-butoxide

Produkt 1

HCID 86694329tert-butyl (3R)-4-(5-fluoro-6-methylpyridin-2-yl)-3-methylpiperazine-1-carboxylateAusbeute 95,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)KatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a mixture of 500 mg of 6-bromo-3-fluoro-2-methylpyridine, 580 mg of tert-butyl (3R)-3-methylpiperazine-1-carboxylate, 506 mg of sodium tert-butoxide, and 61 mg of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and 7.5 mL of toluene was added 48 mg of tris(dibenzylidenacetone)dipalladium (0), followed by stirring at 110° C. for 3 hours. After cooling to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to obtain 780 mg of tert-butyl (3R)-4-(5-fluoro-6-methylpyridin-2-yl)-3-methylpiperazine-1-carboxylate.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-ea53b8ac4d754d359f1c144f130b2d37
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822448B2

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