Sodium Carbonate → 2-benzyl-4-(3,4-dimethoxyphenyl)isoquinolin-1(2H)-one

HRID 918904Notes

Reaction equation

HRID 918904 reaction equation
[CH2:1]([N:8]1[CH:17]=[C:16](Br)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24](C2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29].C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[CH:17]=[C:16]([C:25]2[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[C:27]([O:28][CH3:29])[CH:26]=2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 708927422-benzyl-4-bromoisoquinolin-1(2H)-oneHCID 867235802-(3,4-Dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3-dioxolane

Product 1

HCID 766837452-benzyl-4-(3,4-dimethoxyphenyl)isoquinolin-1(2H)-oneYield 86.4%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of 2-benzyl-4-bromoisoquinolin-1(2H)-one (0.377 g, 1.20 mmol), 2-(3,4-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3-dioxolane (0.380 g, 1.44 mmol) and Na2CO3 (0.382 g, 3.60 mmol) was degassed under nitrogen. Toluene (20 mL), ethanol (20 mL) and water (2 mL) were then added. The reaction mixture was degassed again and Pd(PPh3)4 (0.139 g, 0.12 mmol) was added. The reaction was stirred at 90° C. for 16 h under nitrogen. After that time, the mixture was cooled to rt and concentrated under reduced pressure. The residue was diluted with water (50 mL) and extracted with ethyl acetate (2×100 mL). The organic phase was washed with water, brine, dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 70:30 hexanes/ethyl acetate to 60:40 hexanes/ethyl acetate) to give 2-benzyl-4-(3,4-dimethoxyphenyl)isoquinolin-1(2H)-one (0.385 g, 86%) as a pale yellow solid: mp 174-176° C.; 1H NMR (400 MHz, CDCl3): δ 8.57 (d, J=7.81 Hz, 1H), 7.47-7.66 (m, 3H), 7.24-7.42 (m, 5H), 7.06 (s, 1H), 6.85-6.98 (m, 3H), 5.27 (s, 2H), 3.93 (s, 3H), 3.87 (s, 3H). ESI MS m/z 372 [M+H]+.

Workup

  1. customwas degassed under nitrogen
  2. additionToluene (20 mL), ethanol (20 mL) and water (2 mL) were then added
  3. customThe reaction mixture was degassed again
  4. temperatureAfter that time, the mixture was cooled to rt
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was diluted with water (50 mL)
  7. extractionextracted with ethyl acetate (2×100 mL)
  8. washThe organic phase was washed with water, brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe product was purified by flash column chromatography (silica gel, 70:30 hexanes/ethyl acetate to 60:40 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-185f678cee1149938df8e3ebdee03abb
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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