Ethanol → N-(2-phenyl-pyridin-3-yl)-acetamide hydrochloride

HRID 429516Notes

Reaction equation

HRID 429516 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9](=[O:11])[CH3:10])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[ClH:1].[C:12]1([C:2]2[C:7]([NH:8][C:9](=[O:11])[CH3:10])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 4338791N-(2-chloropyridin-3-yl)acetamide

Product 1

HCID 18356427N-(2-phenyl-pyridin-3-yl)-acetamide hydrochlorideYield 857.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a mixture of N-(2-chloro-pyridin-3-yl)-acetamide (50,0 g, 29.3 mmol), phenylboronic acid (39.3 g, 32.2 mmol), sodium carbonate (49.7 g, 46.9 mmol), in toluene (400 mL), ethanol (100 mL), and water (200 mL) was added tetrakis(triphenylphosphine)palladium(0) (1.02 g, 0.883 mmol). The reaction mixture was heated to reflux for 8 hours, cooled to room temperature, and the layers were separated. The aqueous layer was extracted with ethyl acetate (500 mL) and the organic extracts were combined and concentrated to a yellow solid. The crude solid was dissolved in methanol (500 mL) and concentrated hydrochloric acid was added (10 mL). The solution was concentrated to a low volume and tetrahydrofuran (500 mL) was added. The solid was triturated, filtered and dried to afford N-(2-phenyl-pyridin-3-yl)-acetamide hydrochloride (62.5 g, 86%). M. p.=262-263° C. 1H NMR (300 MHz, DMSOd6) δ2.52 (s, 3), 6.30 (bs, 2), 7.64-7.72 (m, 6), 7.78 (dd, 1, J=1.2, 8.6), 8.06 (dd, 1, J=1.2, 5.2)

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 8 hours
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with ethyl acetate (500 mL)
  5. concentrationconcentrated to a yellow solid
  6. dissolutionThe crude solid was dissolved in methanol (500 mL)
  7. additionconcentrated hydrochloric acid was added (10 mL)
  8. concentrationThe solution was concentrated to a low volume and tetrahydrofuran (500 mL)
  9. additionwas added
  10. customThe solid was triturated
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-7016d57fbc0f439f834b70af1fa13868
Source dataset
uspto-grants-2001_11
Patent number
US06316632B1

Reaction notes

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