Water → HCID 24852342, compound

HRID 1009339Notes

Reaction equation

HRID 1009339 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16](/[CH:24]=[CH:25]/[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]4)=[C:28]([O:38][CH3:39])[CH:27]=3)[N:17]3[CH2:22][CH2:21][O:20][C:19](=[O:23])[C:18]=23)=[CH:10][CH:9]=1.O.[OH-].[Na+].[CH2:43]1COCC1>CO>[F:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[N:15]=[C:16](/[CH:24]=[CH:25]/[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]4)=[C:28]([O:38][CH3:39])[CH:27]=3)[N:17]3[CH2:22][CH2:21][O:20][CH2:19][C:18]=23)=[CH:12][CH:13]=1.[F:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[N:15]=[C:16](/[CH:24]=[CH:25]/[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]4)=[C:28]([O:38][CH3:39])[CH:27]=3)[N:17]([CH2:22][CH2:21][OH:20])[C:18]=2[CH2:19][O:23][CH3:43])=[CH:12][CH:13]=1

Participants

8

Reactant 5

HCID 962Water2×HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 24852341HCID 24852341, compound

Product 2

HCID 24852342HCID 24852342, compoundHCID 58970100HCID 58970100, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

LAH (1 mg) was added to a solution of 1-(4-fluorophenyl)-3-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6-dihydroimidazo[5,1-c][1,4]oxazin-8-one (5 mg) in THF (1 mL), and the reaction solution was stirred at room temperature for 30 minutes. Water (0.01 mL), a 5 N sodium hydroxide solution (0.01 mL), water (0.03 mL) and methanol (5 mL) were sequentially added to the reaction solution. The suspension was filtered through celite, and the filtrate was concentrated under reduced pressure. p-Toluenesulfonic acid monohydrate (6 mg) was added to a solution of the resulting residue in toluene (5 mL) and DMF (1 mL), and the reaction solution was stirred at 120° C. for 2.5 hours. The reaction solution was left to cool to room temperature. Then, ethyl acetate and saturated sodium bicarbonate water were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: ethyl acetate->ethyl acetate:methanol=5:1) to obtain 1 mg of 1-(4-fluorophenyl)-3-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6-dihydro-8H-imidazo[5,1-c][1,4]oxazine and 2 mg of 2-{4-(4-fluorophenyl)-5-methoxymethyl-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}imidazol-1-yl}ethanol.

Workup

  1. filtrationThe suspension was filtered through celite
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionp-Toluenesulfonic acid monohydrate (6 mg) was added to a solution of the resulting residue in toluene (5 mL)
  4. stirringDMF (1 mL), and the reaction solution was stirred at 120° C. for 2.5 hours
  5. waitThe reaction solution was left
  6. temperatureto cool to room temperature
  7. additionThen, ethyl acetate and saturated sodium bicarbonate water were added to the reaction solution
  8. customthe organic layer was separated
  9. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: ethyl acetate->ethyl acetate:methanol=5:1)

Sources & evidence

ORD record
ord-e084c90a379b4adcb42dedfd71286f61
Source dataset
uspto-grants-2011_07
Patent number
US07973033B2

Reaction notes

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