Potassium Carbonate → N-{5-[(1S)-1-azidoethyl]pyridin-3-yl}-3-methylbenzamide

HRID 572215Notes

Reaction equation

HRID 572215 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]([NH2:9])=[O:8])[CH:2]=1.[N:11]([C@H:14]([C:16]1[CH:17]=[N:18][CH:19]=[C:20](Br)[CH:21]=1)[CH3:15])=[N+:12]=[N-:13].CN(C)CCN.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.[Cu]I>[N:11]([C@H:14]([C:16]1[CH:21]=[C:20]([NH:9][C:7](=[O:8])[C:3]2[CH:4]=[CH:5][CH:6]=[C:1]([CH3:10])[CH:2]=2)[CH:19]=[N:18][CH:17]=1)[CH3:15])=[N+:12]=[N-:13]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 66053N,N-DimethylethylenediamineHCID 69253m-ToluamideHCID 866418603-[(1S)-1-azidoethyl]-5-bromopyridine

Product 1

HCID 86641861N-{5-[(1S)-1-azidoethyl]pyridin-3-yl}-3-methylbenzamideYield 28.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (1R)-1-(5-bromopyridin-3-yl)ethanol (10 mmol) in tetrahydrofuran (40 mL), cooled to 0° C., was added diphenylphosphoryl azide (4.3 mL, 20 mmol) in one portion followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (3 mL, 20 mmol) dropwise over 30 minutes. After this time the reaction mixture was allowed to warm slowly to room temperature and was stirred overnight. The mixture was diluted with ethyl acetate (50 mL) and water (50 mL), the two phases separated and the aqueous phase extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine (50 mL), dried (MgSO4) and concentrated under reduced pressure to give a black liquid which was purified by flash chromatography (silica, ethyl acetate/hexanes) to give 3-[(1S)-1-azidoethyl]-5-bromopyridine (1.7 g, 75%) as a colourless liquid. A mixture of m-toluamide (164 mg, 1.21 mmol), 3-[(1S)-1-azidoethyl]-5-bromopyridine (227 mg, 1 mmol), copper (I) iodide (9.6 mg, 0.05 mmol), N,N-dimethylethylene diamine (0.011 mL, 0.1 mmol) and potassium carbonate (276 mg, 2 mmol) in dioxane (1 mL) was heated in a microwave reactor at 110° C. for 30 minutes then at 160° C. for a further 30 minutes. After this time the mixture was allowed to cool to room temperature, was diluted with ethyl acetate (5 mL) and was filtered through Celite. The filtrate was concentrated under reduced pressure to give a brown oil which was purified by flash chromatography (silica, ethyl acetate/dichloromethane) to give N-{5-[(1S)-1-azidoethyl]pyridin-3-yl}-3-methylbenzamide (80 mg, 28%) as a colourless oil.

Workup

  1. temperatureto cool to room temperature
  2. filtrationwas filtered through Celite
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto give a brown oil which
  5. customwas purified by flash chromatography (silica, ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-dc36b65e04e64d7297fe9c5bc0262b9d
Source dataset
uspto-grants-2015_05
Patent number
US09029386B2

Reaction notes

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