Ethyl Acrylate → (E)-tert-Butyl 6-(3-ethoxy-3-oxoprop-1-enyl)-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4'-piperidine]-1'-carboxylate

HRID 2172058Notes

Reaction equation

HRID 2172058 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH2:3].C(N(C(C)C)CC)(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:40]1[CH:41]=[C:42]2[C:59](=[N:60][CH:61]=1)[NH:58][C:57](=[O:62])[C:44]1([CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH2:45]1)[CH2:43]2>C(#N)CC.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:6]([O:5][C:1](=[O:4])/[CH:2]=[CH:3]/[C:40]1[CH:41]=[C:42]2[C:59](=[N:60][CH:61]=1)[NH:58][C:57](=[O:62])[C:44]1([CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:54])([CH3:55])[CH3:56])=[O:51])[CH2:46][CH2:45]1)[CH2:43]2)[CH3:7]

Participants

8

Reactant 4

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742041Tert-butyl 6-bromo-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4'-piperidine]-1'-carboxylate

Product 1

HCID 67154730(E)-tert-Butyl 6-(3-ethoxy-3-oxoprop-1-enyl)-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4'-piperidine]-1'-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

Ethyl acrylate (2.3 mL, 21.2 mmol), diisopropylethylamine (3.7 mL, 21.2 mmol) and P(o-tolyl)3 (323 mg, 1.06 mmol) were successively added to a suspension of tert-butyl 6-bromo-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4′-piperidine]-1′-carboxylate (2.10 g, 5.3 mmol) in propionitrile (20 mL) and dimethylformamide (5 mL) in a sealed tube. The resulting mixture was then purged with argon prior to the addition of palladium acetate (120 mg, 0.53 mmol). The mixture was purged with argon again and refluxed overnight. The reaction mixture was then filtered on Celite®. The filtrate was concentrated to dryness and the residue was solubilized in dichloromethane (100 mL). The resulting solution was washed with a saturated solution of ammonium chloride (100 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was precipitated in dichloromethane/diethylether/pentane, the title product was obtained as an off-white solid (1.52 g, 70%).

Workup

  1. customThe resulting mixture was then purged with argon
  2. customThe mixture was purged with argon again
  3. temperaturerefluxed overnight
  4. filtrationThe reaction mixture was then filtered on Celite®
  5. concentrationThe filtrate was concentrated to dryness
  6. washThe resulting solution was washed with a saturated solution of ammonium chloride (100 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue was precipitated in dichloromethane/diethylether/pentane

Sources & evidence

ORD record
ord-2702c2b5b6e8472795c690e9dcbc68c7
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

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