Triphenylphosphine → Methyl 4-oxo-4-[(5-vinyl-2-pyridyl)amino]butanoate

HRID 525995Notes

Reaction equation

HRID 525995 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:6][CH:7]=1.[C:17]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:18]=1.C([Sn](CCCC)(CCCC)C=C)CCC>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[O:16]=[C:9]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([CH:17]=[CH2:18])=[CH:7][N:6]=1)[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 81998TributylvinyltinHCID 1506825Methyl 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoate

Product 1

HCID 89443936Methyl 4-oxo-4-[(5-vinyl-2-pyridyl)amino]butanoateYield 15%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 15220664Palladium--triphenylphosphane (1/1)CatalystHCID 1140TolueneSolvent

Procedure

To a solution of methyl 4-[(5-bromo-2-pyridyl)amino]-4-oxo-butanoate (commercially available: 0.25 g, 0.871 mmol) in toluene (10 mL) was added palladium; triphenylphosphane (0.101 g, 0.0871 mmol) and tributyl(vinyl)stannane (0.33 g, 0.30 mL, 1.04 mmol). The reaction mixture was refluxed overnight. Then, 0.05 eq of palladium triphenylphosphane and 0.6 eq of tritutylvinylstannane were added. Volatiles were removed under vacuum and residue taken up in acetonitrile. The acetonitrile phase was washed twice with hexane and concentrated under vacuum. The residue was purified by flash chromatography eluting with cyclohexane-ethyl acetate (3/1) to give methyl 4-oxo-4-[(5-vinyl-2-pyridyl)amino]butanoate (compound A40) (0.20 g, 15%). 1H NMR (400 MHz, CDCl3) 8.26 (s, 1H), 8.19 (sb, 1H), 8.15 (m, 2H), 7.76 (m, 1H), 6.65 (m, 1H), 5.34 (d, 1H), 5.30 (d, 1H), 3.72 (s, 3H), 2.75 (m, 4H) ppm.

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. customVolatiles were removed under vacuum and residue
  3. washThe acetonitrile phase was washed twice with hexane
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by flash chromatography
  6. washeluting with cyclohexane-ethyl acetate (3/1)

Sources & evidence

ORD record
ord-06549fbd826b44eea2e0a24b88ab1f05
Source dataset
uspto-grants-2016_05
Patent number
US09345244B2

Reaction notes

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