2-Bromopyridine → 2-Cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)-4-pyridin-2-ylbutanamide

HRID 561863

Reaktionsgleichung

Reaktionsgleichung von HRID 561863
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([Li])CCC.C(SCCCC)CCC.[C:22](/[C:24](=[CH:40]\[C:41]1[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][O:50][C:51]2[C:56]([Cl:57])=[CH:55][C:54]([CH3:58])=[CH:53][C:52]=2[Cl:59])=[CH:43][CH:42]=1)/[C:25]([N:27]([CH:37]1[CH2:39][CH2:38]1)[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:30]=1[CH3:36])=[O:26])#[N:23]>C1COCC1.CCOCC>[C:22]([CH:24]([CH:40]([C:41]1[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][O:50][C:51]2[C:52]([Cl:59])=[CH:53][C:54]([CH3:58])=[CH:55][C:56]=2[Cl:57])=[CH:43][CH:42]=1)[CH2:8][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)[C:25]([N:27]([CH:37]1[CH2:38][CH2:39]1)[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:30]=1[CH3:36])=[O:26])#[N:23]

Komponenten

7

Edukt 4

HCID 79732-BromopyridineHCID 11002Dibutyl sulfideHCID 66761334HCID 66761334, VerbindungHCID 178418339Butyllithium

Produkt 1

HCID 667612652-Cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)-4-pyridin-2-ylbutanamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a THF solution (0.5 M) of 2-bromopyridine (2.8 eq.) was added, at −78° C., n-butyl lithium (1.6 M hexane solution, 2.8 eq.) dropwise over 15 min. The resulting yellow suspension was stirred at −78° C. for a further 15 min before an ether solution (0.5 M) of cuprous iodide (1.4 eq.) and dibutyl sulfide (2.8 eq.) was added over 15 min. The resulting reaction mixture was allowed to stir at −78° C. for 15 min and then at 0° C. for 15 min. Finally, to this was added dropwise at 0° C., a THF solution (0.1 M) of (2E)-2-cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)acrylamide (Example 1, Step 2, 1 eq.). The resulting emerald green suspension was stirred at 0° C. for 15 min and then at RT for 2 h. The reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl:conc. aq. NH4OH solution and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. The crude product thus obtained was purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc). The title compound was isolated as a mixture of diastereomers.

Aufarbeitung

  1. additionwas added over 15 min
  2. customThe resulting reaction mixture
  3. waitat 0° C. for 15 min
  4. additionFinally, to this was added dropwise at 0° C.
  5. stirringThe resulting emerald green suspension was stirred at 0° C. for 15 min
  6. waitat RT for 2 h
  7. customThe reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl
  8. extractionaq. NH4OH solution and extracted with ether
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated in vacuo
  13. customThe crude product thus obtained
  14. customwas purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-1414afcd05de430599c7a232a9ddb81b
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063105B2

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