Cesium carbonate → Methyl 5-hydroxybenzofuran-2-carboxylate

HRID 984109Notes

Reaction equation

HRID 984109 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]2[CH:13]=[CH:12][C:11](S)=[CH:10][C:8]=2[CH:9]=1)=[O:4].ClCC1SC(C2C=CC(C(F)(F)F)=CC=2)=NC=1C.C(=O)([O-])[O-:34].[Cs+].[Cs+]>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]2[CH:13]=[CH:12][C:11]([OH:34])=[CH:10][C:8]=2[CH:9]=1)=[O:4]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27830065-Chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-thiazoleHCID 207660115-Mercapto-benzofuran-2-carboxylic acid methyl ester

Product 1

HCID 12208973Methyl 5-hydroxybenzofuran-2-carboxylateYield 152.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 5-mercapto-benzofuran-2-carboxylic acid methyl ester (300 mg, 1.4 mmol) and 5-chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole (550 mg, 1.9 mmol) was dissolved in 5 ml anhydrous acetonitrile followed by addition of cesium carbonate (700 mg, 2.1 mmol). The reaction was then stirred at 60° C. for 2 hours, filtered and concentrated in vacuo. Purification by flash column chromatography (gradient elution: 5% EtOAc/hexanes to 45% EtOAc/hexanes), gave the title compound (410 mg, 61%) as a pale yellow solid. M.p. 132-133° C.; IR (thin film) cm−1: 1731; 400 MHz 1H NMR (DMSO-d6) δ 7.95 (d, 2H, J=8.1 Hz), 7.79 (s, 1H), 7.74 (d, 2H, J=8.1 Hz), 7.65 (m, 2H), 7.51 (d, 1H, J=9.0 Hz), 4.44 (s, 2H), 3.82 (s, 3H); MS m/z 464 (M+1); Anal. Calc'd for C22H16F3N1O3S2 C, 57.01; H, 3.48; N, 3.02, found: C, 56.94; H, 3.44; N, 2.84.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. customPurification
  4. washby flash column chromatography (gradient elution: 5% EtOAc/hexanes to 45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-abe5283618a04c02854c78282b6c0bbf
Source dataset
uspto-grants-2005_03
Patent number
US06867224B2

Reaction notes

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