1-Phenethylamine, (+)- → 4-(2,3-Dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-({[(1r)-1-phenylethyl]amino}methyl)-2-pentanol

HRID 418780

Reaktionsgleichung

Reaktionsgleichung von HRID 418780
[C:1]1([C@H:7]([NH2:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:10][C:11]([C:21]1[C:29]2[O:28][CH2:27][CH2:26][C:25]=2[CH:24]=[CH:23][CH:22]=1)([CH3:20])[CH2:12][C:13]1([C:16]([F:19])([F:18])[F:17])[CH2:15][O:14]1>CCO>[O:28]1[C:29]2[C:21]([C:11]([CH3:20])([CH3:10])[CH2:12][C:13]([CH2:15][NH:9][C@@H:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH3:8])([OH:14])[C:16]([F:18])([F:19])[F:17])=[CH:22][CH:23]=[CH:24][C:25]=2[CH2:26][CH2:27]1

Komponenten

4

Edukt 2

HCID 6431891-Phenethylamine, (+)-HCID 577755187-[1,1-Dimethyl-2-(2-trifluoromethyloxiranyl)ethyl]-2,3-dihydrobenzofuran

Produkt 1

HCID 156045864-(2,3-Dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-({[(1r)-1-phenylethyl]amino}methyl)-2-pentanolAusbeute 104,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To an ice-cooled solution of (R)-(+)-1-phenylethylamine (4.43 mL, 34.9 mmol) in anhydrous EtOH (3 mL) was added, dropwise, racemic 7-{1,1-dimethyl-2-[2-(trifluoromethyl)-2-oxiranyl]ethyl}-2,3-dihydro-1-benzofuran (1 g, 3.49 mmol), which may be prepared according to WO04/063163. The reaction mixture was then heated at 50° C. overnight, cooled to room temperature and evaporated in vacuo. The residue was applied to a 50 g silica SPE cartridge and eluted with 0.5% NH3 in toluene. The appropriate fractions were combined and evaporated in vacuo to give a colourless oil (1.486 g). This oil was subjected to mass-directed autopreparation to give Intermediate 22 (2S isomer, 314 mg), Intermediate 23 (2R isomer, 334 mg) plus a mixed fraction (480 mg). The mixed fraction was re-subjected to mass-directed autopreparation to give further Intermediate 22 (90 mg), Intermediate 23 (125 mg) plus a mixed fraction (160 mg). The fractions containing Intermediate 22 were combined with each other as were the fractions containing Intermediate 23.

Aufarbeitung

  1. additionwas added
  2. temperaturecooled to room temperature
  3. customevaporated in vacuo
  4. washeluted with 0.5% NH3 in toluene
  5. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-4f37f6bd241642809b6a11ea4d1cfac7
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093281B2

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