Sodium hydride → 1-Acetyl-4-ethynyl-4-(2-nitrophenoxy)piperidine

HRID 2232328Notes

Reaction equation

HRID 2232328 reaction equation
[Na+].CS([CH2-])=O.[H-].[Na+].[C:8]([N:11]1[CH2:16][CH2:15][C:14]([C:18]#[CH:19])([OH:17])[CH2:13][CH2:12]1)(=[O:10])[CH3:9].F[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N+:27]([O-:29])=[O:28]>O.CS(C)=O>[C:8]([N:11]1[CH2:16][CH2:15][C:14]([C:18]#[CH:19])([O:17][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[N+:27]([O-:29])=[O:28])[CH2:13][CH2:12]1)(=[O:10])[CH3:9]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 738951-Fluoro-2-nitrobenzeneHCID 10154010Methane, sulfinylbis-, ion(1-), sodiumHCID 132167351-(4-Ethynyl-4-hydroxypiperidin-1-yl)ethan-1-one

Product 1

HCID 142814881-Acetyl-4-ethynyl-4-(2-nitrophenoxy)piperidineYield 24%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a stirred solution of dimsyl sodium, prepared from 16.5 g of sodium hydride (50% in oil, washed three times with hexanes) and 400 ml of dimethylsulfoxide at 17°-25° was added, in aliquots, 57.7 g of 1-acetyl-4-ethynyl-4-piperidinol. Upon completion of the addition, 55.3 g of 2-fluoronitrobenzene was added dropwise at a rate such that the temperature remained below 25°. The mixture was stirred at room temperature for 20 min, poured into cold water, extracted three times with ether, washed with saturated sodium chloride solution and dried over anhydrous potassium carbonate. Filtration followed by evaporation of solvent provided an oil, which crystallized on standing. Recrystallization from ethyl acetate/cyclohexane provided 23.6 g (24%) of product, mp 112°-115°.

Workup

  1. additionwas added dropwise at a rate such that the temperature
  2. customremained below 25°
  3. extractionextracted three times with ether
  4. washwashed with saturated sodium chloride solution
  5. dry with materialdried over anhydrous potassium carbonate
  6. filtrationFiltration
  7. customfollowed by evaporation of solvent
  8. customprovided an oil, which
  9. customcrystallized
  10. customRecrystallization from ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-840872052e3443169b1fb9f66316fc8a
Source dataset
uspto-grants-1988_11
Patent number
US04788201

Reaction notes

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