Cesium carbonate → (E)-N-(4-methoxybenzyl)-4-styrylpicolinamide

HRID 572643Notes

Reaction equation

HRID 572643 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=[O:9])[CH:3]=1.CC1(C)C(C)(C)OB(/[CH:28]=[CH:29]/[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][NH:10][C:8](=[O:9])[C:4]2[CH:3]=[C:2](/[CH:28]=[CH:29]/[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:7]=[CH:6][N:5]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 57084134,4,5,5-tetramethyl-2-((E)-2-phenylethenyl)-1,3,2-dioxaborolaneHCID 709784674-bromo-N-(4-methoxybenzyl)picolinamide

Product 1

HCID 86675903(E)-N-(4-methoxybenzyl)-4-styrylpicolinamideYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a flask containing 4-bromo-N-(4-methoxybenzyl)picolinamide (0.3 g) in 1,4-dioxane (1.1 mL) was added (E)-4,4,5,5-tetramethyl-2-styryl-1,3,2-dioxaborolane (0.22 g), Pd(dppf)—chloroform adduct (0.04 g) and 2M aqueous cesium carbonate (1.9 mL). The mixture was stirred at about 95° C. for about 12 h. The reaction was diluted with water and washed three times with CH2Cl2. The organic solution was filtered over Celite®, and concentrated under reduced pressure yielding (E)-N-(4-methoxybenzyl)-4-styrylpicolinamide as a deep yellow oil (0.25 g, 80%). LC/MS (Table-1, Method f) Rt=2.03 min; MS m/z 345 (M+H)+. This intermediate was then dissolved in 4.3 mL of 1,4-dioxane and treated with 0.87 mL of water and sodium periodate (0.75 g). After stirring for approximately 30 min at RT, osmium tetroxide (0.30 mL of a 0.1 M solution in t-butanol) was added to the reaction which was then stirred for about an additional 4 h at RT. The layers were separated and the organic solution was dried over MgSO4, filtered, and concentrated under reduced pressure. The product was isolated by flash chromatography to give 4-formyl-N-(4-methoxybenzyl)picolinamide (0.25 g, 80%): LC/MS (Table 1, method-f) Rt=1.01 min; MS m/z 271 (M+H)+.

Workup

  1. washwashed three times with CH2Cl2
  2. filtrationThe organic solution was filtered over Celite®
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c322d0f40e5942d3b0dd9dc99626a43a
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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