(1,1'-Biphenyl)-2-ol → 2-Quinoxalin-6-yl-malonic acid diethyl ester

HRID 1921654Notes

Reaction equation

HRID 1921654 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[N:5]2.[CH2:12]([O:14][C:15](=[O:22])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:13].C1(C2C=CC=CC=2)C(O)=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.[Cu](I)I.O>[CH2:12]([O:14][C:15](=[O:22])[CH:16]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[N:5]2)[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:13]

Participants

8

Reactant 4

HCID 7017(1,1'-Biphenyl)-2-olHCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 242717656-Iodoquinoxaline

Product 1

HCID 674275872-Quinoxalin-6-yl-malonic acid diethyl ester

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-iodo-quinoxaline (0.323 g, 1.26 mmol), malonic acid diethyl ester (0.404 g, 2.52 mmol), copper iodide (0.012 g, 0.063 mmol), biphenyl-2-ol (0.021 g, 0.126 mmol) and cesium carbonate (0.616 g, 1.89 mmol) in THF (5 mL) was heated to 70° C. in a sealed tube for 24 hours. The solution was then cooled to room temperature, water was added and the crude product was extracted from ethyl acetate. The product was purified via silica gel column chromatography in hexane:ethyl acetate (1:1) to give 2-quinoxalin-6-yl-malonic acid diethyl ester. 2-quinoxalin-6-yl-malonic acid diethyl ester (0.066 g, 0.229 mmol) was added to a solution of sodium hydroxide [2N] (0.229 mL) in methanol (2 mL) and stirred for several hours at room temperature. The reaction was then evaporated in vacuo, 1N HCl was added and the product was extracted with ethyl acetate to give 0.030 g (70%) of quinoxalin-6-yl-acetic acid. 1H NMR (400 MHz, DMSO-d6) δ 12.6 (bs, 1H), 8.93 (dd, 2H, J=2.0, 6.0 Hz), 8.05 (d, 1H, 8.8 Hz), 7.99 (m, 1H), 7.79 (dd, 1H, J=2.0, 8.8 Hz), 3.89 (s, 2H).

Workup

  1. extractionthe crude product was extracted from ethyl acetate
  2. customThe product was purified via silica gel column chromatography in hexane:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-9fcd53be0c464d679f77027dc9b5c3bd
Source dataset
uspto-grants-2012_05
Patent number
US08173654B2

Reaction notes

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