Acetonitrile → 1-(6-Phenylpyridin-3-yl)ethanone

HRID 1048842Notes

Reaction equation

HRID 1048842 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7](Br)=[N:8][CH:9]=1)(=[O:3])[CH3:2].[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])([O-])=O.[Na+].[Na+].C(#N)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[C:11]1([C:7]2[N:8]=[CH:9][C:4]([C:1](=[O:3])[CH3:2])=[CH:5][CH:6]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 156681955-Acetyl-2-bromopyridine

Product 1

HCID 123018821-(6-Phenylpyridin-3-yl)ethanoneYield 52%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

5-acetyl-2-bromopyridine 38 (0.656 g, 3.28 mmol), phenylboronic acid (0.800 g, 6.56 mmol), Na2CO3 (0.243 g, 2.29 mmol), Pd(PPh3)2Cl2 (0.115 g, 0.16 mmol, 5% Pd), acetonitrile (26 mL) and H2O (26 mL) were added to 50 mL screw cap pressure vessel. The mixture was stirred, degassed by purging with argon for 15 min, sealed and placed in an 80° C. oil bath for 14 h (overnight). The dark colored mixture was cooled and extracted with ether. The organic layer was filtered through a pad of celite, rinsed with ether, washed with brine, dried over MgSO4 and filtered. The filtrate was concentrated and the residue purified by flash column chromatography (SiO2, 20 g, 5% EtOAc/hexanes) to afford the coupled ketone 40 as a white solid (0.33 g, 52%): TLC Rf=0.4 (25% EtOAc/hexanes); mp 124.9126.2° C.; 1H NMR (500 MHz, CDCl3) δ 9.22 (d, J=2.0 Hz, 1H), 8.28 (dd, J=8.3, 2.2 Hz, 1H), 8.10-7.99 (m, 2H), 7.83 (d, J=8.3 Hz, 1H), 7.55-7.40 (m, 3H), 2.65 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 196.6, 161.1, 150.2, 138.2, 136.7, 130.9, 130.4, 129.2, 127.6, 120.4, 26.9; IR (neat cm−1) 3062, 2999, 2960, 2322, 1673, 1557, 1382, 1016, 736; HRMS (DART, M++H) m/z 198.0906 (calculated for C13H12NO, 198.0919).

Workup

  1. customscrew cap pressure vessel
  2. customdegassed
  3. customby purging with argon for 15 min
  4. customsealed
  5. customplaced in an 80° C.
  6. customfor 14 h
  7. custom(overnight)
  8. temperatureThe dark colored mixture was cooled
  9. extractionextracted with ether
  10. filtrationThe organic layer was filtered through a pad of celite
  11. washrinsed with ether
  12. washwashed with brine
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated
  16. customthe residue purified by flash column chromatography (SiO2, 20 g, 5% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c0568a80a4ee453bb4cec5db7b36ab17
Source dataset
uspto-grants-2016_07
Patent number
US09382213B2

Reaction notes

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