Methanol → Methyl {(2S,4R)-1-[(1S)-5-(benzyloxy)-4-methyl-1-(3,3,3-trifluoropropyl)pent-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate

HRID 1942302Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1942302
C[CH:2]([C@@H:6]1[CH2:11][CH2:10][NH:9][C@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[CH2:7]1)[C:3]([O-:5])=[O:4].[CH3:22][CH:23]([C:33]#[CH:34])[CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[F:35][C:36]([F:42])([F:41])[CH2:37][CH2:38][CH:39]=O.[CH3:43]O>O.[Au](Br)(Br)Br>[CH2:26]([O:25][CH2:24][CH:23]([CH3:22])[C:33]#[C:34][C@@H:39]([N:9]1[CH2:10][CH2:11][C@@H:6]([CH2:2][C:3]([O:5][CH3:43])=[O:4])[CH2:7][C@H:8]1[C:12]1[CH:13]=[CH:14][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:16][CH:17]=1)[CH2:38][CH2:37][C:36]([F:42])([F:41])[F:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Komponenten

7

Edukt 4

HCID 887MethanolHCID 27770834,4,4-TrifluorobutanalHCID 59201193{[(2-Methylbut-3-yn-1-yl)oxy]methyl}benzeneHCID 86617999(+)-methyl{(2S,4R)-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate2×

Produkt 1

HCID 59201240Methyl {(2S,4R)-1-[(1S)-5-(benzyloxy)-4-methyl-1-(3,3,3-trifluoropropyl)pent-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 82525Gold tribromideKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of (+)-methyl {(2S,4R)-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Intermediate 2, 440 mg, 1.460 mmol), {[(2-methylbut-3-yn-1-yl)oxy]methyl}benzene (509 mg, 2.92 mmol), 4,4,4-trifluorobutyraldehyde (368 mg, 2.92 mmol) and gold(III) bromide (63.8 mg, 0.146 mmol) were combined in water (1.5 ml) in a 5 ml microwave vial. The vial was sealed and the mixture was stirred and heated at 70° C. in the microwave. After cooling to RT, the mixture was diluted with MeOH and then loaded on to a SCX cartridge (2 g). The cartridge was washed with MeOH (5×10 ml), then the product was eluted with 2N NH3 in MeOH (5×10 ml). The NH3/MeOH fractions were combined and evaporated. The residue was partitioned between EtOAc/H2O. The aqueous layer was extracted with EtOAc (×3). The combined extracts were washed with brine (×1), dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography (silica, 5-10% EtOAc/isohexane) to give the title compound (562 mg, mixture of diasteromers) as a colourless oil. M/Z 584 (MH+).

Aufarbeitung

  1. customThe vial was sealed
  2. temperatureAfter cooling to RT
  3. washThe cartridge was washed with MeOH (5×10 ml)
  4. washthe product was eluted with 2N NH3 in MeOH (5×10 ml)
  5. customevaporated
  6. customThe residue was partitioned between EtOAc/H2O
  7. extractionThe aqueous layer was extracted with EtOAc (×3)
  8. washThe combined extracts were washed with brine (×1)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by chromatography (silica, 5-10% EtOAc/isohexane)

Quellen und Nachweise

ORD-Eintrag
ord-4b7d89b7b0da4efd85732d9f0e029169
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389547B2

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