Water → 4-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-one

HRID 2252833Notes

Reaction equation

HRID 2252833 reaction equation
[Cl-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)[CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)C=CC=CC=1.[O:28]=[C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]([CH:39]=O)=[CH:31][NH:30]1.O>C1COCC1>[N:12]1[CH:13]=[CH:14][CH:15]=[C:10]([CH:9]=[CH:39][C:32]2[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:29](=[O:28])[NH:30][CH:31]=2)[CH:11]=1

Participants

5

Reactant 3

HCID 962WaterHCID 179632241-Oxo-1,2-dihydroisoquinoline-4-carbaldehydeHCID 22325077Triphenyl(3-pyridylmethyl)phosphonium chloride

Product 1

HCID 692072474-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Under an N2 atmosphere, 147 g (377 mmol) of triphenyl-(pyridin-3-yl-methyl)-phosphonium chloride in 2.2 l of THF are mixed with 44.1 g (393 mmol) of potassium-tert-butylate and stirred for 30 min. The suspension is heated to 50° C. and a mixture of 50.0 g (289 mmol) of 1-oxo-1,2-dihydro-isoquinoline-4-carbaldehyde and 2.2 l of THF is added dropwise and finally stirred for 10 h at 60° C. To the cooled reaction mixture is added 700 ml of water and then the THF is evaporated off on a RE. The residue is taken up in 5 l of water and 8 l of EtOAc, the water phase is separated and extracted 3 more times with EtOAc. The organic phases are washed with water and with brine, combined, dried (Na2SO4) and left to stand over night. A solid separates from the mixture and is filtered off and washed with EtOAc[→(E) 4-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-one]. The filtrate is extracted twice with 1 N HCl and then discarded. The acidic aqueous phases are immediately rendered basic with sat. Na2CO3 solution and extracted 3 times with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2, EtOAc/ethanol 19:1→9:1) yields first of all (Z) 4-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-one, followed by an (E/Z) mixture of 4-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-one. (E) 4-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-on: m.p. 222-224° C.; 1H NMR (DMSO-d6) δ 11.57 (sb, HN), 8.80 (s, 1H), 8.44 (d, 1H), 8.26 (d, 1H), 8.12 (m, 2H), 7.79 (t, 1H), 7.68 (d, J=16.3 Hz, 1H), 7.56 (m, 2H), 7.39 (dd, 1H), 7.07 (d, J=16.3 Hz, 1H). (Z) 4-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-one: 1H NMR (DMSO-d6) δ 11.24 (sb, HN), 8.39 (s, 1H), 8.32 (d, 1H), 8.25 (d, 1H), 7.71 (t, 1H), 7.65 (d, 1H), 7.54 (m, 2H), 7.21 (dd, 1H), 6.90 (s, 1H), 6.81 (s, 2HOlef.).

Workup

  1. additionis added dropwise
  2. stirringfinally stirred for 10 h at 60° C
  3. customTo the cooled reaction mixture
  4. customthe THF is evaporated off on a RE
  5. custom8 l of EtOAc, the water phase is separated
  6. extractionextracted 3 more times with EtOAc
  7. washThe organic phases are washed with water and with brine
  8. dry with materialdried (Na2SO4)
  9. waitleft
  10. waitto stand over night
  11. filtrationA solid separates from the mixture and is filtered off
  12. washwashed with EtOAc[→(E) 4-[2-(pyridin-3-yl)-vinyl]-2H-isoquinolin-1-one]
  13. extractionThe filtrate is extracted twice with 1 N HCl
  14. extractionextracted 3 times with EtOAc
  15. washThe organic phases are washed with water and brine
  16. dry with materialdried (Na2SO4)
  17. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-a84a66e0a6fd4231aa6a5963ad0a9987
Source dataset
uspto-grants-2008_01
Patent number
US07323474B2

Reaction notes

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