Potassium Carbonate → (9-(3-(2-Hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 446453Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 446453
Cl.[CH:2]([C:5]1[S:6][CH:7]=[C:8]([C:10]([N:12]2[CH2:17][C:16]3([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[O:15][CH2:14][CH2:13]2)=[O:11])[N:9]=1)([CH3:4])[CH3:3].Br[CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([CH2:32][CH2:33][OH:34])[CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[OH:34][CH2:33][CH2:32][C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[CH2:25][CH2:24][N:20]1[CH2:19][CH2:18][C:16]2([O:15][CH2:14][CH2:13][N:12]([C:10]([C:8]3[N:9]=[C:5]([CH:2]([CH3:4])[CH3:3])[S:6][CH:7]=3)=[O:11])[CH2:17]2)[CH2:22][CH2:21]1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 581685432-(3-(2-Bromoethyl)phenyl)ethanolHCID 66964119(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride

Produkt 1

HCID 58168488(9-(3-(2-Hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A mixture of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride [Example 27, step a] (13.6 g) and 2-(3-(2-bromoethyl)phenyl)ethanol [Organometallics 2002, 21(20), 4217] (13.51 g) and potassium carbonate (21.7 g) in acetonitrile (700 mL) and water (13 mL) was heated at 60° C. for 36 hours. The solvent was decanted off and evaporated under reduced pressure. The residue was partitioned between ethyl acetate and brine, the aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were dried, filtered and the solvent evaporated under reduced pressure. The residue was purified by flash silica chromatography, using 5% methanol in ethyl acetate containing 1% triethylamine as solvent. Fractions containing the product were evaporated to dryness to afford the subtitled compound. Yield 13.2 g.

Aufarbeitung

  1. customThe solvent was decanted off
  2. customevaporated under reduced pressure
  3. customThe residue was partitioned between ethyl acetate and brine
  4. extractionthe aqueous layer was re-extracted with ethyl acetate
  5. customthe combined organic layers were dried
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe residue was purified by flash silica chromatography
  9. additionFractions containing the product
  10. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-0be6952b7b9945b99756625975e58e8f
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476265B2

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