Diisopropylethylamine → [5-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone

HRID 493223Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 493223
[Cl:1][C:2]1[C:3]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]2)=[CH:4][C:5]2[O:9][C:8]([C:10]([OH:12])=O)=[C:7]([CH3:13])[C:6]=2[CH:14]=1.Cl.[F:26][C:27]1([F:33])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>C1COCC1>[Cl:1][C:2]1[C:3]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]2)=[CH:4][C:5]2[O:9][C:8]([C:10]([N:30]3[CH2:31][CH2:32][C:27]([F:33])([F:26])[CH2:28][CH2:29]3)=[O:12])=[C:7]([CH3:13])[C:6]=2[CH:14]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 687236205-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid

Produkt 1

HCID 68724082[5-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanoneAusbeute 99,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

In a flask were mixed together the above prepared 5-chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid (0.200 g, 0.406 mmol, corrected for purity), 4,4-difluoropiperidine hydrochloride (0.077 g, 1.2 eq.), (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (0.216 g, 1.2 eq.) and 2.4 eq. of N-ethyldiisopropylamine (0.166 mL) in 4 mL of abs. THF and stirred over night at ambient temperature. Pouring onto crashed ice/AcOEt/NH4Cl-solution, twofold extraction with AcOEt, washing with water and brine, drying over magnesium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, NEt3/AcOEt=2/98) yielded 0.183 g of the title compound as white solid.

Aufarbeitung

  1. additionIn a flask were mixed together the
  2. additionPouring
  3. extractionextraction with AcOEt
  4. washwashing with water and brine
  5. dry with materialdrying over magnesium sulfate, and evaporation of the solvents

Quellen und Nachweise

ORD-Eintrag
ord-f1c4c54cb962482e9be32388a8bbddfc
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07534788B2

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