Sodium Hydroxide → HCID 19778072, compound

HRID 2082306Notes

Reaction equation

HRID 2082306 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([N:8]2[CH2:13][CH2:12][CH:11]([C:14](O)=O)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[C:19](Cl)(=[O:23])[C:20](Cl)=O.[CH2:25]([Mg]Br)[CH2:26][CH2:27]CC.[Cl-].[NH4+].[OH-].[Na+]>C(Cl)Cl.O1CCCC1.CCOCC.[Cu]I.CN(C)C=O>[F:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][C:19](=[O:23])[CH2:20][CH2:25][CH2:26][CH3:27])[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1

Participants

11

Reactant 5

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 7780751-(4-fluorobenzoyl)piperidine-4-carboxylic acidHCID 178445865HCID 178445865, compound

Product 1

HCID 19778072HCID 19778072, compound

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

1-(4-Fluorobenzoyl)piperidine-4-carboxylic acid (11.31 g, 45.0 mmol) is dissolved in methylene chloride (100 mL) at 0° C., and dimethylformamide (0.20 mL) and oxalyl chloride (5.8 g, 46 mmol) are added. The mixture is stirred 3 hr at room temperature, after which the solvent is evaporated; toluene (50 mL) is added and evaporated under reduced pressure. The toluene treatment is then repeated. In a second flask, copper (I) iodide (8.57 g, 45.0 mmol) is suspended in tetrahydrofuran (100 mL) at -78° C. under a nitrogen atmosphere. Methylithium (1.55M in ether, 29 mL, 45 mmol) is added, and the mixture is stirred at room temperature for 50 min. The mixture is cooled to -78° C., and pentylmagnesium bromide (2.0M in ether, 22.5 mL, 45 mmol) is added. The mixture is stirred for 15 min at -78° C., 1.5 hr at room temperature, and is cooled to -78° C. A solution of the first residue in tetrahydrofuran (30 mL) is added to the second mixture dropwise over 30 min, and the mixture is stirred 1 hr at -78° C., and then 3 hr at room temperature. The mixture is poured into saturated ammonium chloride (500 mL), sodium hydroxide (1 g) is added, and the mixture is stirred 16 hr. The layers are separated, the aqueous phase is extracted twice with methylene chloride, and the combined organics are washed twice with 1N sodium hydroxide, once with brine, dried over magnesium sulfate, and evaporated. The residue is chromatographed on silica gel eluting with hexane and ethyl acetate mixtures and recrystallized from ether-petroleum ether to afford the title compound.

Workup

  1. customafter which the solvent is evaporated
  2. additiontoluene (50 mL) is added
  3. customevaporated under reduced pressure
  4. stirringthe mixture is stirred at room temperature for 50 min
  5. temperatureThe mixture is cooled to -78° C.
  6. stirringThe mixture is stirred for 15 min at -78° C., 1.5 hr at room temperature
  7. temperatureis cooled to -78° C
  8. stirringthe mixture is stirred 1 hr at -78° C.
  9. custom3 hr
  10. customat room temperature
  11. additionis added
  12. stirringthe mixture is stirred 16 hr
  13. customThe layers are separated
  14. extractionthe aqueous phase is extracted twice with methylene chloride
  15. washthe combined organics are washed twice with 1N sodium hydroxide, once with brine
  16. dry with materialdried over magnesium sulfate
  17. customevaporated
  18. customThe residue is chromatographed on silica gel eluting with hexane and ethyl acetate mixtures
  19. customrecrystallized from ether-petroleum ether

Sources & evidence

ORD record
ord-23b7b7cde74f46818637b2ac3ebebd1f
Source dataset
uspto-grants-1993_02
Patent number
US05189036

Reaction notes

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