Benzylamine → (3aR,4R,5S,7aS)-2-benzyl-5-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(4-fluorophenyl)octahydro-1H-isoindole

HRID 1991363Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1991363
CS(O[CH2:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([O:13][C@@H:14]([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[CH3:15])[C@@H:9]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C@@H:8]1[CH2:37]OS(C)(=O)=O)(=O)=O.[CH2:43]([NH2:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(O)C>[CH2:43]([N:50]1[CH2:37][C@@H:8]2[C@H:7]([CH2:12][CH2:11][C@H:10]([O:13][C@@H:14]([C:16]3[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[C:18]([C:26]([F:28])([F:27])[F:29])[CH:17]=3)[CH3:15])[C@H:9]2[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH2:6]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Komponenten

4

Edukt 2

HCID 7504BenzylamineHCID 42639485HCID 42639485, Verbindung

Produkt 1

HCID 42639648(3aR,4R,5S,7aS)-2-benzyl-5-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(4-fluorophenyl)octahydro-1H-isoindole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

In a pressure tube was placed a solution of crude [(1S,2R,3R,4S)-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)cyclohexane-1,2-diyl]di(methylene) dimethanesulfonate (step H) in ˜20 mL ethanol and 1.2 mL (˜3 equiv.) benzylamine. The pressure tube was sealed and heated at 150° C. in an oil bath for 3 hr. The tube was cooled to RT and opened. The resulting mixture was transferred to a round bottom flask and the solvent removed under vacuum. The residue was diluted with 100 mL EtOAc, washed with 20 mL 5N aq. NaOH, dried over MgSO4 drying agent, filtered and the solvent was evaporated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with EtOAc to give 1.6 g of the title compound. 1H-NMR (CDCl3): δ: 7.35-7.20 (5H, m), 7.50 (2H, s), 6.97 (2H, m), 6.85 (2H, t, J=8.2 Hz), 4.42 (1H, t, J=6.0 Hz), 3.75 (2H, d, J=13.4 Hz), 3.50 (2H, d, J=13.4 Hz), 3.30 (1H, m), 2.96 (1H, m), 2.52 (3H, m), 2.19 (2H, m), 1.98 (1H, m), 1.97 (1H, m), 1.86 (2H, m),.1.57 (1H, m), 1.33 (3H, t, J=6.0 Hz), 1.30 (1H, m). MS: (MH)+566.0.

Aufarbeitung

  1. customIn a pressure tube was placed
  2. customThe pressure tube was sealed
  3. temperatureThe tube was cooled to RT
  4. customThe resulting mixture was transferred to a round bottom flask
  5. customthe solvent removed under vacuum
  6. additionThe residue was diluted with 100 mL EtOAc
  7. washwashed with 20 mL 5N aq. NaOH
  8. dry with materialdried over MgSO4 drying agent
  9. filtrationfiltered
  10. customthe solvent was evaporated under vacuum
  11. customThe residue was purified by flash column chromatography on silica gel eluting with EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-fde0443989cc47b1ae9340e9f640d888
Quelldatensatz
uspto-grants-2010_01
Patentnummer
US07645790B2

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