Water → HCID 66961044, compound

HRID 2247620Notes

Reaction equation

HRID 2247620 reaction equation
[H-].[Na+].[Cl:3][CH2:4][CH2:5][CH2:6][CH:7](P(OCC)(OCC)=O)[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[F:23][C:24]1[CH:31]=[C:30]([N:32]2[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]2)[C:29]([O:38][CH3:39])=[CH:28][C:25]=1[CH:26]=O.O>C1COCC1.C(OCC)(=O)C>[Cl:3][CH2:4][CH2:5][CH2:6]/[C:7](=[CH:26]\[C:25]1[CH:28]=[C:29]([O:38][CH3:39])[C:30]([N:32]2[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]2)=[CH:31][C:24]=1[F:23])/[C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 730140352-fluoro-5-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehydeHCID 86602480Tert-butyl 5-chloro-2-(diethoxyphosphoryl)valerate

Product 1

HCID 66961044HCID 66961044, compoundYield 106.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (containing mineral oil at 40%, 0.68 g) was added to a solution of tert-butyl 5-chloro-2-(diethoxyphosphoryl)valerate (5.59 g) in THF (50 mL) in a nitrogen atmosphere at room temperature, and the reaction solution was stirred at room temperature for 30 minutes. A solution of 2-fluoro-5-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (3.19 g) in THF (10 mL) was added to the reaction mixture, and the reaction solution was stirred at room temperature for 4 hours. Water and ethyl acetate were added to the reaction mixture and the organic layer was partitioned. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (elution solvent: heptane-ethyl acetate system) to obtain tert-butyl (E)-5-chloro-2-(2-fluoro-5-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valerate (5.93 g). A solution of tert-butyl (E)-5-chloro-2-(2-fluoro-5-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valerate in trifluoroacetic acid (30 mL) was stirred while cooling with ice. After 2 hours, the reaction solution was concentrated under reduced pressure. Tert-butyl methyl ether was added to the resulting residue, and the resulting deposited solid was filtered to obtain 3 g of the title compound. Properties data of the compound are as follows.

Workup

  1. stirringthe reaction solution was stirred at room temperature for 4 hours
  2. customthe organic layer was partitioned
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel chromatography (elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-cb5aa38236104ffea31f41f1fc963b75
Source dataset
uspto-grants-2010_03
Patent number
US07687640B2

Reaction notes

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