Carbon Dioxide → 6-Methoxy-2-(4-methoxyphenyl)-3-carboxybenzo[b]thiophene

HRID 2305302Notes

Reaction equation

HRID 2305302 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10](Br)=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[S:8][C:7]=2[CH:20]=1.[Li]CCCC.[C:26](=[O:28])=[O:27]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:26]([OH:28])=[O:27])=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[S:8][C:7]=2[CH:20]=1

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 8509423-Bromo-6-methoxy-2-(4-methoxyphenyl)-benzo[b]thiopheneHCID 178418339Butyllithium

Product 1

HCID 154806536-Methoxy-2-(4-methoxyphenyl)-3-carboxybenzo[b]thiopheneYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

6-Methoxy-2-(4-methoxyphenyl)-3-bromobenzo[b]thiophene (15.0 g, 42.9 mmol) was dissolved in 300 mL of anhydrous THF under N2 and cooled to −70° C. To this solution was added nBuLi (29.6 mL, 47.4 mmol, 1.6 M solution in hexanes) dropwise via syringe. After stirring at −70° C. for 20 min, a steady stream of CO2 (g) was introduced into the reaction mixture for 15 min. The mixture was allowed to gradually warm to 0° C. and then quenched by pouring the mixture into cold 1 N HCl (500 mL). The aqueous layer was extracted with EtOAc (3×300 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to a solid. The crude product was chromatographed (SiO2, 25% EtOAc/hexanes) to provide 9.35 g (69%) of 6-methoxy-2-(4-methoxyphenyl)-3-carboxybenzo[b]thiophene as a white solid. mp 166-170° C. 1H NMR (DMSO-d6) δ (doubling due to rotamers) 13.0-12.8 (bs), 8.10 and 7.68 (d, J=8.1 Hz, 1H), 7.63 and 7.47 (d, J=8.6 Hz, 2H), 7.59 and 7.54 (d, J=2.0 Hz, 1H), 7.10 and 6.97 (dd, J=8.1, 2.0 Hz, 1H), 7.02 (d, J=8.6 Hz, 2H), 3.83 and 3.79 (s, 3H), 3.82 and 3.80 (s, 3H). FD mass spec: 315. Anal. Calcd. for C17H14O4S: C, 64.95; H, 4.49. Found: C, 65.19; H, 4.32.

Workup

  1. temperatureto gradually warm to 0° C.
  2. customquenched
  3. additionby pouring the mixture into cold 1 N HCl (500 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (3×300 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated in vacuo to a solid
  7. customThe crude product was chromatographed (SiO2, 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8982489e63904e0da7dd70e9fb39c9f7
Source dataset
uspto-grants-2002_08
Patent number
US06440958B1

Reaction notes

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