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

HRID 82906Notes

Reaction equation

HRID 82906 reaction equation
[C:1]([O:5][C:6]([CH3:9])([CH3:8])[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:42]1[CH:43]=[C:44]2[C:61](=[N:62][CH:63]=1)[NH:60][C:59](=[O:64])[C:46]1([CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][CH2:47]1)[CH2:45]2>C(#N)CC.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:6]([O:5][C:1](=[O:4])/[CH:2]=[CH:3]/[C:42]1[CH:43]=[C:44]2[C:61](=[N:62][CH:63]=1)[NH:60][C:59](=[O:64])[C:46]1([CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:56])([CH3:57])[CH3:58])=[O:53])[CH2:48][CH2:47]1)[CH2:45]2)([CH3:9])([CH3:8])[CH3:7]

Participants

8

Reactant 4

HCID 15458tert-Butyl 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 68338142(E)-tert-Butyl 6-(3-tert-butoxy-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

Tert-Butyl acrylate (3.9 mL, 26.8 mmol), diisopropylethylamine (2.46 mL, 14.1 mmol) and P(o-tolyl)3 (409 mg, 1.34 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 (2.66 g, 6.7 mmol) in propionitrile (107 mL) and dimethylformamide (40 mL) in a sealed tube. The resulting mixture was then purged with argon prior to the addition of palladium acetate (151 mg, 0.673 mmol). The mixture was purged with argon again and refluxed overnight. The reaction mixture was then filtered on Celite® and the cake was washed with DCM (50 mL). The filtrate was concentrated to dryness and the residue was triturated with dichloromethane. The title product was obtained as a light grey solid (1.83 g, 61%, py 79.9%).

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. washthe cake was washed with DCM (50 mL)
  6. concentrationThe filtrate was concentrated to dryness
  7. customthe residue was triturated with dichloromethane

Sources & evidence

ORD record
ord-909967f5c256491b8232f06033bb41ed
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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