p-Toluenesulfonic acid monohydrate → Hydroxy-[2-(4-methoxy-phenyl)-6-methyl-imidazo[1,2-a]pyridin-3-yl]-acetic acid ethyl ester

HRID 858893Notes

Reaction equation

HRID 858893 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]3[CH:18]=2)=[CH:5][CH:4]=1.C1(C)C=CC=CC=1.[C:26]([O:30][CH2:31][CH3:32])(=[O:29])[CH:27]=[O:28].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:31]([O:30][C:26](=[O:29])[CH:27]([OH:28])[C:18]1[N:12]2[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:11]2=[N:10][C:9]=1[C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)[CH3:32]

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 7359102-(4-Methoxyphenyl)-6-methylimidazo[1,2-a]pyridineHCID 86599969Ethyl glyoxylate toluene

Product 1

HCID 58763627Hydroxy-[2-(4-methoxy-phenyl)-6-methyl-imidazo[1,2-a]pyridin-3-yl]-acetic acid ethyl esterYield 20%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a magnetically stirred solution of 2-(4-methoxy-phenyl)-6-methyl-imidazo[1,2-a]pyridine 13a (2.55 g, 10.71 mmol) and ethyl glyoxylate toluene solution (11.79 mL, 54.62 mmol) in toluene (130 mL) under Ar atmosphere was added p-toluenesulfonic acid monohydrate (60.9 mg, 0.32 mmol). The reaction mixture was equipped with a dean-stark trap and refluxed for 4 h. The mixture was cooled to room temperature and concentrated in vacuo. The crude product was purified by column chromatography over silica gel (40:60 EtOAc/hexane, then 100% EtOAc as eluent), which gave the title compound (0.72 g, 20%) as an off white solid. 1H NMR (400 MHz, CDCl3) 1.15 (t, J=7.0 Hz, 3H), 2.31 (s, 3H), 3.83 (s, 3H), 4.13 (m, 1H), 4.24 (m, 1H), 5.75 (s, 1H), 6.91 (d, J=8.8 Hz, 2H), 7.04 (dd, J=1.4, 9.1 Hz, 1H), 7.47 (d, J=9.1 Hz, 1H), 7.60 (d, J=8.8 Hz, 2H), 7.99 (s, 1H).

Workup

  1. customThe reaction mixture was equipped with a dean-stark trap
  2. temperaturerefluxed for 4 h
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by column chromatography over silica gel (40:60 EtOAc/hexane

Sources & evidence

ORD record
ord-9b51e107fd504eb6bef33feb77a26f5a
Source dataset
uspto-grants-2006_12
Patent number
US07148353B2

Reaction notes

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