Sodium Hydroxide → Nicotinamide

HRID 404759Notes

Reaction equation

HRID 404759 reaction equation
FC1C=CC([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][C:13](Cl)=[N:12][CH:11]=2)=CC=1.Br.BrCC1C=CC=CN=1.[OH-].[Na+].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[C:9]([NH2:8])(=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[N:12][CH:11]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 2653166HCID 2653166, compoundHCID 2723671Tetrabutylammonium HydroxideHCID 27347202-(Bromomethyl)pyridine hydrobromide

Product 1

HCID 936NicotinamideYield 269.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

In a round bottom flask, N-(4-fluoro-phenyl)-6-chloro-nicotinamide (0.905 g, 3.62 mmol) and 2-bromomethyl-pyridine hydrobromide (0.915 g, 3.62 mmol) was suspended in toluene (5 ml). 50% aqueous sodium hydroxide (2.0 mL) was added to the reaction mixture, followed by tetra-n-butyl-ammonium hydroxide (100 ul). The biphasic reaction mixture was vigorously stirred overnight, and the aqueous layer removed by pipette. The organic layer was diluted with ethyl acetate (20 mL) and washed with water, saturated aqueous sodium chloride and dried over sodium sulfate. The organic layer was filtered and removed by rotary evaporation to yield 1.19 g (96%) of nicotinamide intermediate X as an off white solid. ESI-MS m/z=341.9, 343.9 [M+H]+.

Workup

  1. customThe biphasic reaction mixture
  2. customthe aqueous layer removed by pipette
  3. additionThe organic layer was diluted with ethyl acetate (20 mL)
  4. washwashed with water, saturated aqueous sodium chloride
  5. dry with materialdried over sodium sulfate
  6. filtrationThe organic layer was filtered
  7. customremoved by rotary evaporation

Sources & evidence

ORD record
ord-f2fa7ada1d254762b2d45f4da0fe6e5a
Source dataset
uspto-grants-2014_06
Patent number
US08748623B2

Reaction notes

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