Methyl pyruvate → HCID 66961054, compound

HRID 1362760Notes

Reaction equation

HRID 1362760 reaction equation
C([N-]C(C)C)(C)C.[Li+].[F:9][CH:10](P(=O)(OCC)OCC)[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]2)=[C:13]([O:23][CH3:24])[CH:12]=1.[C:33]([O:38][CH3:39])(=[O:37])[C:34]([CH3:36])=O.O.C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C>[F:9][C:10]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]2)=[C:13]([O:23][CH3:24])[CH:12]=1)=[C:34]([CH3:36])[C:33]([O:38][CH3:39])=[O:37]

Participants

7

Reactant 4

HCID 11748Methyl pyruvateHCID 2724682Lithium diisopropylamideHCID 86585896Sodium bicarbonate waterHCID 86602494HCID 86602494, compound

Product 1

HCID 66961054HCID 66961054, compoundYield 41.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

Diethyl (fluoro-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)methyl)phosphonate (1.1 g) was obtained from 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (1 g) in accordance with the method described in Tetrahedron Letters, 1996, vol. 37, no. 5, p. 629. Lithium diisopropylamide (1.5 M solution in THF, 0.25 mL) was added to a solution of the resulting diethyl (fluoro-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)methyl)phosphonate (110 mg) in THF at −78° C., and the reaction solution was stirred at −78° C. for 2 hours. Methyl pyruvate (32 mg) was added to the reaction solution at −78° C. The reaction solution was stirred at −78° C. for 15 minutes, and then further stirred at room temperature for 45 minutes. Saturated sodium bicarbonate water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 39 mg of methyl 3-fluoro-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-2-methylacrylate as a mixture of isomers (E) and (Z). Properties data of the compounds are as follows.

Workup

  1. stirringThe reaction solution was stirred at −78° C. for 15 minutes
  2. stirringfurther stirred at room temperature for 45 minutes
  3. customthe organic layer was partitioned
  4. dry with materialThe resulting organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (elution solvent: heptane:ethyl acetate=1:1->ethyl acetate)

Sources & evidence

ORD record
ord-6386b686f98842a28c643c18d3fec20c
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

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