Water → HCID 24781181, compound

HRID 553953Notes

Reaction equation

HRID 553953 reaction equation
C(N(S(F)(F)[F:7])CC)C.[F:10][C:11]1[CH:12]=[C:13]([C@@H:19]2[CH2:28][C@@H:27](O)[CH2:26][C@@H:25]3[N:20]2[C:21](=[O:45])/[C:22](=[CH:30]/[C:31]2[CH:36]=[CH:35][C:34]([N:37]4[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]4)=[C:33]([O:43][CH3:44])[CH:32]=2)/[CH2:23][CH2:24]3)[CH:14]=[C:15]([F:18])[C:16]=1[F:17].O.C(OCC)(=O)C>ClCCl>[F:7][C@@H:27]1[CH2:26][C@@H:25]2[N:20]([C:21](=[O:45])/[C:22](=[CH:30]/[C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]4)=[C:33]([O:43][CH3:44])[CH:32]=3)/[CH2:23][CH2:24]2)[C@H:19]([C:13]2[CH:14]=[C:15]([F:18])[C:16]([F:17])=[C:11]([F:10])[CH:12]=2)[CH2:28]1.[CH3:44][O:43][C:33]1[CH:32]=[C:31]([CH:36]=[CH:35][C:34]=1[N:37]1[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]1)/[CH:30]=[C:22]1\[CH2:23][CH2:24][C@H:25]2[N:20]([C:21]\1=[O:45])[C@H:19]([C:13]1[CH:14]=[C:15]([F:18])[C:16]([F:17])=[C:11]([F:10])[CH:12]=1)[CH:28]=[CH:27][CH2:26]2.[CH3:44][O:43][C:33]1[CH:32]=[C:31]([CH:36]=[CH:35][C:34]=1[N:37]1[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]1)/[CH:30]=[C:22]1\[CH2:23][CH2:24][C@H:25]2[N:20]([C:21]\1=[O:45])[C@H:19]([C:13]1[CH:14]=[C:15]([F:18])[C:16]([F:17])=[C:11]([F:10])[CH:12]=1)[CH2:28][CH:27]=[CH:26]2

Participants

8

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 123472(Diethylamino)sulfur trifluorideHCID 24781611HCID 24781611, compound

Product 3

HCID 24781181HCID 24781181, compoundHCID 24781182HCID 24781182, compoundHCID 24781183HCID 24781183, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethylaminosulfur trifluoride (301 μL) was added to a solution of (E)-(6S,8S,9aR)-6-(3,4,5-trifluorophenyl)-8-hydroxy-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]octahydroquinolizin-4-one that is an optically active compound obtained above with a retention time of 4.4 minutes (228 mg) in dichloromethane (20 mL) under ice-cooling, and the reaction solution was stirred at room temperature overnight. Crushed ice, water, and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) and CHIRALPAK™ AD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: ethanol-hexane system) to obtain (E)-(6S,8R,9aR)-8-fluoro-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-6-(3,4,5-trifluorophenyl)octahydroquinolizin-4-one (69 mg), (E)-(6S,9aR)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-6-(3,4,5-trifluorophenyl)-1,2,3,6,9,9a-hexahydroquinolizin-4-one (125 mg), and (E)-(6S,9aR)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-6-(3,4,5-trifluorophenyl)-1,2,3,6,7,9a-hexahydroquinolizin-4-one (1.8 mg). The property values of (E)-(6S,8R,9aR)-8-fluoro-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-6-(3,4,5-trifluorophenyl)octahydroquinolizin-4-one are as follows.

Workup

  1. temperaturecooling
  2. customthe organic layer was separated
  3. washThe resulting organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) and CHIRALPAK™ AD-H

Sources & evidence

ORD record
ord-b61f119fba634859a179934c58a96fc4
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

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