Dimethylformamide → 1-(2-Chloro-pyridin-3-yl)-1H-pyrrole-2-carbaldehyde

HRID 251983Notes

Reaction equation

P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[C:12]([N:13]2[CH:17]=[CH:16][CH:15]=[CH:14]2)=[CH:11][CH:10]=[CH:9][N:8]=1.[OH-].[Na+].CN(C)[CH:22]=[O:23]>>[Cl:6][C:7]1[C:12]([N:13]2[CH:17]=[CH:16][CH:15]=[C:14]2[CH:22]=[O:23])=[CH:11][CH:10]=[CH:9][N:8]=1

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 14798Sodium Hydroxide

HCID 24813Phosphorus oxychloride

HCID 27579082-chloro-3-pyrrol-1-ylpyridine

Product 1

HCID 27723241-(2-Chloro-pyridin-3-yl)-1H-pyrrole-2-carbaldehydeYield 80.5%

Procedure

To 14.6 g of N,N-dimethylformamide was added dropwise 8.3 g of phosphorus oxychloride under ice-cooling. The mixture was stirred at room temperature for 30 minutes. Thereto 6.5 g of 1-(2-chloro-3-pyridinyl)-1H-pyrrole was added, and the resulting mixture was stirred at 60° C. for 2 hours. The reaction mixture was allowed to cool to room temperature, and added to ice water. The mixture was adjusted to pH 4 by an addition of a 2N aqueous sodium hydroxide solution, and then extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 6.05 g of 1-(2-chloro-3-pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula:

Workup

temperaturecooling
stirringthe resulting mixture was stirred at 60° C. for 2 hours
temperatureto cool to room temperature
extractionextracted with ethyl acetate two times
washwashed successively with water
dry with materialan aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-508fd031a2b3434baf247771b08c6682
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07867949B2

Reaction notes

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