Hydrochloric Acid → HCID 86749409, compound

HRID 2295192Notes

Reaction equation

HRID 2295192 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].[Li]CCCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:26]=[C:25]([CH3:35])[C:24]=2/[CH:36]=[CH:37]/[CH:38]=[O:39])=[CH:19][CH:18]=1.Cl.C([O-])(O)=O.[Na+]>C1COCC1.O.CCCCCC.CCOC(C)=O.CCOCC>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:26]=[C:25]([CH3:35])[C:24]=2/[CH:36]=[CH:37]/[CH:38]([OH:39])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[CH:19][CH:18]=1

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 21471346HCID 21471346, compoundHCID 178418339Butyllithium

Product 1

HCID 86749409HCID 86749409, compoundYield 29.1%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl acetoacetate (324 mg, 2.79 mmol) was added dropwise to a slurry of NaH (60% in mineral oil, 111.7 mg, 2.79 mmol) in dry THF (7 ml) at 0° C. After 15 minutes, n-BuLi (1.5M in hexanes, 1.46 ml, 2.19 mmol) was added and the mixture was stirred an additional 15 minutes. Addition of a solution of (E)-3-[4-(4-fluorophenyl)-2-methyl-6-phenyl-3-pyridinyl]-2-propenal (633 mg, 1.99 mmol) in THF (7 ml) to the reaction mixture resulted in the formation of a bright red solution. Twenty minutes after the addition, the solution was poured into a biphasic mixture of Et2O (40 ml) and 1N HCl (5.5 ml) in H2O (20 ml). The aqueous layer was made basic with saturated NaHCO3 and the phases were separated. The aqueous layer was extracted again with Et2O, neutralized with 1N HCl and extracted once more. The combined Et2O layers were washed with brine, dried (Na2SO4), filtered and stripped to yield an oil. Flash chromatography (Merck SiO2, 1:1 EtOAc:hexane) afforded (E)-7-[4-(4-fluorophenyl)-2-methyl-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester (251 mg, 29%) as a yellow oil

Workup

  1. customresulted in the formation of a bright red solution
  2. additionTwenty minutes after the addition
  3. customthe phases were separated
  4. extractionThe aqueous layer was extracted again with Et2O
  5. extractionextracted once more
  6. washThe combined Et2O layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customto yield an oil

Sources & evidence

ORD record
ord-e4212d1df4984028b119e21e0efc78b6
Source dataset
uspto-grants-1997_11
Patent number
US05691322

Reaction notes

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