Triphenylarsine → 1,1-Dimethylethyl 3′,6′-dihydro[3,4′-bipyridine]-1′(2′H)-carboxylate

HRID 643573Notes

Reaction equation

HRID 643573 reaction equation
FC(F)(F)S(O[C:7]1[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH:12]=1)(=O)=O.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Li+].[Cl-].C([Sn]([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][N:57]=1)(CCCC)CCCC)CCC>CN1C(=O)CCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:57]1[CH:58]=[CH:59][CH:60]=[C:61]([C:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH:12]=2)[CH:56]=1

Participants

7

Reactant 4

HCID 11773TriphenylarsineHCID 433294Lithium ChlorideHCID 6077842-(Tributylstannyl)pyridineHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 589134081,1-Dimethylethyl 3′,6′-dihydro[3,4′-bipyridine]-1′(2′H)-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

tert-Butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate (prepared according to Wustrow, D. J., Wise, L. D., Synthesis, (1991), 993-995; 2.73 g, 8.22 mmol) was dissolved in 80 mL of NMP. Triphenylarsine (220 mg, 0.66 mmol), LiCl (1.09 g, 24.7 mmol), and tris(dibenzylideneacetone)-dipalladium(0) (156 mg, 0.160 mmol) were then added to the reaction vessel. After 10 min of constant stirring, tributylstannyl pyridine (4.0 g, 9.7 mmol) in 10 mL of NMP was added using a syringe. The reaction vessel was repeatedly evacuated and flushed with N2 (g) (4×). The reaction mixture was then stirred at rt for 30 min, then at 80° C. for 2.5 h, and then at 65° C. for 16 h. Afterwards, 20 mL of 1M KF solution was added. The mixture was stirred for 1.5 h and then diluted with ethyl acetate (100 mL) and filtered. The filtrate was further diluted with 200 mL of 1M KF solution and 200 mL of ethyl acetate. The organic and aqueous layers were separated, and the aqueous layer was extracted once again with ethyl acetate (200 mL). The organic layers were combined, washed with water (6×200 mL) and then with brine (1×300 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. Tert-Butyl 3′,6′-dihydro-3,4′-bipyridine-1′(2′H)-carboxylate was obtained through silica gel flash column chromatography (1% MeOH in EtOAc). ESI-MS calculated for C15H20N2O2: 260.35, found 261 (M+H).

Workup

  1. custom, Synthesis, (1991), 993-995
  2. customThe reaction vessel was repeatedly evacuated
  3. customflushed with N2 (g) (4×)
  4. waitat 80° C. for 2.5 h
  5. waitat 65° C. for 16 h
  6. additionAfterwards, 20 mL of 1M KF solution was added
  7. stirringThe mixture was stirred for 1.5 h
  8. additiondiluted with ethyl acetate (100 mL)
  9. filtrationfiltered
  10. additionThe filtrate was further diluted with 200 mL of 1M KF solution and 200 mL of ethyl acetate
  11. customThe organic and aqueous layers were separated
  12. extractionthe aqueous layer was extracted once again with ethyl acetate (200 mL)
  13. washwashed with water (6×200 mL)
  14. dry with materialwith brine (1×300 mL), dried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0e670cb47ac245ef904eabf375b08ec5
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

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