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

HRID 1661830Notes

Reaction equation

HRID 1661830 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-186adc3f71b04d669682d969afba839b
Source dataset
uspto-grants-2011_10
Patent number
US08030305B2

Reaction notes

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