Sodium Carbonate → 2-benzyl-4-(3,4,5-trimethoxyphenyl)isoquinolin-1(2H)-one

HRID 918907Notes

Reaction equation

HRID 918907 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.CC1(C)C(C)(C)OB([C:28]2[CH:33]=[C:32]([O:34][CH3:35])[C:31]([O:36][CH3:37])=[C:30]([O:38][CH3:39])[CH:29]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.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:28]2[CH:29]=[C:30]([O:38][CH3:39])[C:31]([O:36][CH3:37])=[C:32]([O:34][CH3:35])[CH:33]=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

8

Reactant 3

HCID 10340Sodium CarbonateHCID 219239464,4,5,5-Tetramethyl-2-(3,4,5-trimethoxyphenyl)-1,3,2-dioxaborolaneHCID 708927422-benzyl-4-bromoisoquinolin-1(2H)-one

Product 1

HCID 766837462-benzyl-4-(3,4,5-trimethoxyphenyl)isoquinolin-1(2H)-oneYield 55.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-benzyl-4-bromoisoquinolin-1(2H)-one (0.420 g, 1.34 mmol), 4,4,5,5-tetramethyl-2-(3,4,5-trimethoxyphenyl)-1,3,2-dioxaborolane (0.511 g, 1.74 mmol) and Na2CO3 (0.425 g, 4.01 mmol) in toluene (20 mL), ethanol (10 mL) and water (3 mL) was degassed under nitrogen. Pd(PPh3)4 (0.154 g, 0.13 mmol) was then added and the reaction mixture was stirred at 100° C. for 17 h under nitrogen. After that time, the mixture was cooled to rt and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL) and washed with water, brine, dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 90:10 hexanes/ethyl acetate to 75:25 hexanes/ethyl acetate) to give 2-benzyl-4-(3,4,5-trimethoxyphenyl)isoquinolin-1(2H)-one (0.298 g, 55%) as an off white solid: mp 166-168° C.; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=7.8 Hz, 1H), 7.49-7.66 (m, 3H), 7.28-7.41 (m, 5H), 7.08 (s, 1H), 6.57 (s, 2H), 5.28 (s, 2H), 3.91 (s, 3H), 3.85 (s, 6H); ESI MS m/z 402 [M+H]+.

Workup

  1. customwas degassed under nitrogen
  2. temperatureAfter that time, the mixture was cooled to rt
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by flash column chromatography (silica gel, 90:10 hexanes/ethyl acetate to 75:25 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-8f914f8d26a8425bb0695cf06edffc1f
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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