Tributylvinyltin → (R)-1-(3-Vinyl-isoquinolin-6-yl)-ethanol

HRID 1427770Notes

Reaction equation

HRID 1427770 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C@H:12]([OH:14])[CH3:13])=[CH:7][CH:6]=2.[CH2:15]([Sn](CCCC)(CCCC)C=C)[CH2:16]CC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH:15]([C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C@H:12]([OH:14])[CH3:13])=[CH:7][CH:6]=2)=[CH2:16]

Participants

5

Reactant 2

HCID 81998Tributylvinyltin2×HCID 86675864(αR)-3-Chloro-α-methyl-6-isoquinolinemethanol

Product 1

HCID 67960525(R)-1-(3-Vinyl-isoquinolin-6-yl)-ethanolYield 50.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

1,4-Dioxane (5 mL) was degassed with nitrogen, (R)-1-(3-chloro-isoquinolin-6-yl)-ethanol (208 mg, 1 mmol), tributyl(vinyl)tin (951 mg, 0.9 mL, 3 mmol) and bis(triphenylphosphine)palladium(II) dichloride (70 mg, 0.1 mmol) were added and the reaction mixture was heated at 150° C. in a microwave reactor for 1 hour. Additional tributyl(vinyl)tin (0.3 mL, 1 mmol) and bis(triphenylphosphine)palladium(II) dichloride (70 mg, 0.1 mmol) was added and the reaction mixture was heated at 150° C. in a microwave reactor for 1 hour. The reaction mixture was cooled to room temperature and the mixture was filtered thorough filter aid and the filter pad was washed with ethyl acetate. The filtrate was evaporated and the residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 4:1 to 2:1 followed by silica gel chromatography using iso-hexanes/ethyl acetate 3:1 to afford the title compound (100 mg, 50%) as a white solid. 1H NMR (300 MHz, CDCl3) δ1.60 (d, J=6.5 Hz, 3H), 2.11 (brs, 1H), 5.10 (q, J=6.5 Hz, 1H), 5.52 (dd, J=10.6, 1.6 Hz, 1H), 6.40 (dd, J=17.2, 1.6 Hz, 1H), 6.95 (dd, J=17.2, 10.7 Hz, 1H), 7.57 (s, 1H), 7.58 (dd, J=8.5, 1.6 Hz, 1H), 7.78 (brs, 1H), 7.94 (d, J=8.5 Hz, 1H), 9.19 (s, 1H). LCMS (m/z) 200 [M+H], Tr=1.50 min.

Workup

  1. additionwere added
  2. temperaturethe reaction mixture was heated at 150° C. in a microwave reactor for 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationthe mixture was filtered thorough filter aid
  5. washthe filter pad was washed with ethyl acetate
  6. customThe filtrate was evaporated
  7. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-be8316b4b07945f68aa6983d6cc5be5d
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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