(2S)-2,5-Dihydro-2-isopropyl-3,6-dimethoxypyrazine → (2R,5S)-2,5-dihydro-3,6-dimethoxy-2-(2'-fluoro-4'-(trifluoromethyl)benzyl)-5-isopropylpyrazine

HRID 854269Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 854269
[CH3:1][O:2][C:3]1[C@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[CH2:7][N:8]=1.C([Li])CCC.[F:19][C:20]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:21]=1[CH2:22]Br>O1CCCC1>[CH3:10][O:9][C:6]1[C@@H:7]([CH2:22][C:21]2[CH:24]=[CH:25][C:26]([C:28]([F:29])([F:31])[F:30])=[CH:27][C:20]=2[F:19])[N:8]=[C:3]([O:2][CH3:1])[C@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=1

Komponenten

5

Edukt 3

HCID 736065(2S)-2,5-Dihydro-2-isopropyl-3,6-dimethoxypyrazineHCID 27375702-Fluoro-4-(trifluoromethyl)benzyl bromideHCID 178418339Butyllithium

Produkt 1

HCID 20628238(2R,5S)-2,5-dihydro-3,6-dimethoxy-2-(2'-fluoro-4'-(trifluoromethyl)benzyl)-5-isopropylpyrazine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 3.32 g (18 mmol) of commercially available (2S)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine in 100 mL of tetrahydrofuran at −70° C. was added 12 mL (19 mmol) of a 1.6M solution of butyllithium in hexanes. After stirring at this temperature for 20 min, 5 g (19.5 mmol) of 2-fluoro-4-trifluoromethylbenzyl bromide in 20 mL of tetrahydrofuran was added and stirring was continued for 3 h before warming the reaction to ambient temperature. The reaction was quenched with water, concentrated in vacuo, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0-5% ethyl acetate in hexanes) afforded the title compound.

Aufarbeitung

  1. stirringstirring
  2. waitwas continued for 3 h
  3. temperaturebefore warming
  4. customthe reaction to ambient temperature
  5. customThe reaction was quenched with water
  6. concentrationconcentrated in vacuo
  7. extractionextracted with ethyl acetate
  8. washThe combined organic phase was washed with brine
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customPurification by flash chromatography (silica gel, 0-5% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-741ff0731edb49b59db46142dd79c378
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07259160B2

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