Potassium Hydroxide → 4-(3,4-Dimethoxy-2-methoxymethoxyphenyl)-5-nitroisoquinoline

HRID 895674

Reaction equation

HRID 895674 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[N+:12]([O-:14])=[O:13])[CH:5]=[N:4][CH:3]=1.[CH3:15][O:16][C:17]1[C:18]([O:34][CH2:35][O:36][CH3:37])=[C:19](B2OC(C)(C)C(C)(C)O2)[CH:20]=[CH:21][C:22]=1[O:23][CH3:24].[OH-].[K+]>C(COC)OC.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.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>[CH3:15][O:16][C:17]1[C:18]([O:34][CH2:35][O:36][CH3:37])=[C:19]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][C:10]=3[N+:12]([O-:14])=[O:13])[CH:5]=[N:4][CH:3]=2)[CH:20]=[CH:21][C:22]=1[O:23][CH3:24]

Participants

8

Reactant 3

HCID 14797Potassium HydroxideHCID 2712804-Bromo-5-nitroisoquinolineHCID 223807722-(3,4-Dimethoxy-2-methoxymethoxyphenyl)-4,4,5,5-tetramethyl[1,3,2]dioxaborolane

Product 1

HCID 129719194-(3,4-Dimethoxy-2-methoxymethoxyphenyl)-5-nitroisoquinolineYield 99.9%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Isoquinoline 3 (3.36 g; 0.0143 mol), pinacol boronate ester 2 (5.562 g; 0.0172 mol), and 1.0 g (6 mol %) of tetrakis(triphenylphosphine)palladium(0) were suspended in 100 ml of dimethoxyethane (DME). Potassium hydroxide (3.6 g; 0.064 mol), and 0.46 g (10 mol %) of tetrabutylammonium bromide were dissolved in 14.5 ml of water and added to the DME mixture. The resulting suspension was degassed for 30 minutes with argon and then heated at reflux for four hours. The resulting black solution was allowed to cool to room temperature, poured into 500 ml of water, extracted with diethyl ether (3×500 ml), dried (Na2SO4), and concentrated. The product was then purified by column chromatography (silica gel, 50% ethyl acetate: hexane) giving 5.29 g of yellow crystals (80.1%): mp 138-140° C.; 1H NMR: (300 MHz, CDCl3): 9.33 (s, 1H); 8.61 (s, 1H); 8.24 (dd, 1H, J=7.2, 0.9 Hz); 8.0 (dd, 1H, J=6.3, 1.2 Hz); 7.67 (t, 1H, J=7.8 Hz); 7.03 (d, 1H, J=9.6 Hz); 6.81 (d, 1H, J=8.1 Hz); 4.86 (d, 1H, J=6 Hz); 4.70 (d, 1H, J=5.4 Hz); 3.92 (s, 3H); 3.89 (s, 3H); 2.613 (s, 3H). CIMS m/z: 371 (M+H+, 100%). Anal Calc'd for C19H18N2O6: C, 61.62; H, 4.90; N, 7.56. Found: C, 61.66; H, 4.90; N, 7.56.

Workup

  1. customThe resulting suspension was degassed for 30 minutes with argon
  2. temperatureheated
  3. temperatureat reflux for four hours
  4. additionpoured into 500 ml of water
  5. extractionextracted with diethyl ether (3×500 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe product was then purified by column chromatography (silica gel, 50% ethyl acetate: hexane)

Sources & evidence

ORD record
ord-3d757799045d482b8cf3f3b15071a41c
Source dataset
uspto-grants-2005_07
Patent number
US06916832B2

Linked notes

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