Sodium hydride → 1-[(1R,2R)-2-hydroxy-1-(3,4,5-trifluorophenyl)propyl]-3-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}piperidin-2-one

HRID 16327Notes

Reaction equation

HRID 16327 reaction equation
C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.FC(F)(F)C(O)=O.Cl[CH2:28][CH2:29][CH2:30]/[C:31](=[CH:35]\[C:36]1[CH:41]=[CH:40][C:39]([N:42]2[CH:46]=[C:45]([CH3:47])[N:44]=[CH:43]2)=[C:38]([O:48][CH3:49])[CH:37]=1)/[C:32]([OH:34])=O.Cl.[NH2:51][C@H:52]([C:56]1[CH:61]=[C:60]([F:62])[C:59]([F:63])=[C:58]([F:64])[CH:57]=1)[C@H:53]([OH:55])[CH3:54].C(=O)([O-])O.[Na+].[H-].[Na+]>O.C(OCC)(=O)C.CN(C=O)C.C(Cl)CCl>[OH:55][C@H:53]([CH3:54])[C@H:52]([N:51]1[CH2:28][CH2:29][CH2:30]/[C:31](=[CH:35]\[C:36]2[CH:41]=[CH:40][C:39]([N:42]3[CH:46]=[C:45]([CH3:47])[N:44]=[CH:43]3)=[C:38]([O:48][CH3:49])[CH:37]=2)/[C:32]1=[O:34])[C:56]1[CH:57]=[C:58]([F:64])[C:59]([F:63])=[C:60]([F:62])[CH:61]=1

Participants

11

Reactant 6

HCID 24758Sodium hydrideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 66960186(E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetateHCID 68718335(1R,2R)-1-amino-1-(3,4,5-trifluorophenyl)propan-2-ol hydrochloride

Product 1

HCID 687177251-[(1R,2R)-2-hydroxy-1-(3,4,5-trifluorophenyl)propyl]-3-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}piperidin-2-one

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

IPEA (4 mL), HOBT (1.11 g), and EDC (1.57 g) were added to a DMF solution (40 mL) of (E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid trifluoroacetate (CAS Registry No. 870850-40-1, 3.69 g) and (1R,2R)-1-amino-1-(3,4,5-trifluorophenyl)propan-2-ol hydrochloride (1.98 g). This reaction solution was stirred at room temperature for 3.5 hr, and ethyl acetate and a saturated sodium hydrogencarbonate aqueous solution were added thereto. The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained solid was suspended in diisopropyl ether and collected by filtration to give 3.16 g of a condensed substance. To a DMF solution (50 mL) of this condensed substance (3.16 g), sodium hydride (containing 40% mineral oil, 278 mg) was added at 0° C. The resulting reaction solution was stirred at room temperature for 15 min, and ethyl acetate and water were added thereto. The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent: heptane to ethyl acetate) to give 2.3 g of the title compound. The physical property values of this compound were as follows:

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. filtrationcollected by filtration
  5. customto give 3.16 g of a condensed substance
  6. customThe resulting reaction solution
  7. stirringwas stirred at room temperature for 15 min
  8. customThe organic layer was separated
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent: heptane to ethyl acetate)

Sources & evidence

ORD record
ord-27f5abeade7f49f592e818230ef3c442
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Reaction notes

Loading…