Ethyl 3-(trimethylsilyl)propynoate → 1-(2,6-Difluorophenyl)-1-[6-(2,4-difluorophenyl)-5-(hydroxymethyl)pyridin-2-yl]but-3-yn-2-one

HRID 1360706Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1360706
[Si]([O:8][CH2:9][C:10]1[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])=[N:12][C:13]([CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C[Si](C)(C)[C:45]#[C:46][C:47](OCC)=[O:48]>C1COCC1>[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[CH:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][OH:8])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])[N:12]=1)[C:47](=[O:48])[C:46]#[CH:45]

Komponenten

5

Edukt 3

HCID 568601Ethyl 3-(trimethylsilyl)propynoateHCID 2733832Lithium HexamethyldisilazideHCID 577003733-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-6-(2,6-difluorobenzyl)-2-(2,4-difluorophenyl)pyridine

Produkt 1

HCID 577003771-(2,6-Difluorophenyl)-1-[6-(2,4-difluorophenyl)-5-(hydroxymethyl)pyridin-2-yl]but-3-yn-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-(2,6-difluorobenzyl)-2-(2,4-difluorophenyl)pyridine (from Step D above, 4.63 g) in THF was added lithium bis(trimethylsilyl)amide (22.0 mL, 1.0 M in THF) at −78° C. After stirring ½ h at −78° C., ethyl 3-(trimethylsilyl)prop-2-ynoate (2.2 mL) was added. The mixture was warmed to 0° C. and stirred for a couple of hours until reaction complete. The reaction was quenched with 0.1 N HCl, and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and concentrated. The residue in THF was added TBAF (25 mL, 1N in THF) at 0° C. and stirred for 1 h. The solution was washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by silica gel (100% methylene chloride) to give title compound (1.08 g).

Aufarbeitung

  1. temperatureThe mixture was warmed to 0° C.
  2. stirringstirred for a couple of hours until reaction complete
  3. customThe reaction was quenched with 0.1 N HCl
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. additionThe residue in THF was added TBAF (25 mL, 1N in THF) at 0° C.
  9. stirringstirred for 1 h
  10. washThe solution was washed with water, brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel (100% methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-869a02ff46424ae28840243e95de01fb
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07879875B2

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