Sodium Carbonate → HCID 22350424, compound

HRID 896461Notes

Reaction equation

HRID 896461 reaction equation
Br[C:2]1[S:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][CH:6]=1.[CH3:10][C:11]1[S:15][C:14](B(O)O)=[CH:13][CH:12]=1.[C:19]([O-])([O-])=O.[Na+].[Na+].S1C=CC=C1C1SC=CC=1>OS(O)(=O)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[CH3:10][C:11]1[S:15][C:14]([C:2]2[S:3][C:4]([C:7]([O:9][CH3:19])=[O:8])=[CH:5][CH:6]=2)=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 681202,2'-BithiopheneHCID 3491155-Bromothiophene-2-carboxylic acid2×HCID 2734374(5-Methylthiophen-2-yl)boronic acid

Product 1

HCID 22350424HCID 22350424, compound

Reagents, catalysts & solvents 3

HCID 1118Sulfuric AcidCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

In a flask are placed 2-bromothiophene-5-carboxylic acid (1.20 g, 5.81 mmol), 5-methylthiophene-2-boronic acid (0.99 g, 6.97 mmol), and Pd(PPh3)4 (0.20 g, 0.17 mmol). The flask is then vacuum purged and nitrogen filled (3×). THF (12 mL) is then added by syringe followed by vacuum purge and nitrogen fill (3×). A solution of Na2CO3 (2M, 5.8 mL, 11.6 mmol) is added followed by vacuum purge and nitrogen fill (3×). The reaction mixture is heated to reflux for 19 h then cooled to rt and diluted with water. The aqueous solution is extracted with ether (3×). The aqueous layer is then acidified and extracted with EtOAc (3×). The combined organic layers are dried over MgSO4, filtered, and concentrated to provide an inseparable 3:1 mixture of 2-bromothiophene-5-carboxylic acid and bithiophene product. To separate the compounds the methyl esters are formed: In a flask are placed the aforementioned mixture, MeOH (50 mL) and conc H2SO4 (5 drops) and heated to reflux for 24 h. The solution is concentrated and chromatographed over silica gel (2% acetone-heptane) to provide methyl 5′-methyl-2,2′-bithiophene-5-carboxylate as a solid (0.37 g, 26% 2 steps). 1H NMR (400 MHz, CDCl3) δ 7.69, 7.10, 7.07, 6.73, 3.91, 2.52.

Workup

  1. customIn a flask are placed
  2. customvacuum purged
  3. additionnitrogen filled (3×)
  4. additionTHF (12 mL) is then added by syringe
  5. custompurge
  6. custompurge
  7. temperatureThe reaction mixture is heated
  8. temperatureto reflux for 19 h
  9. additiondiluted with water
  10. extractionThe aqueous solution is extracted with ether (3×)
  11. extractionextracted with EtOAc (3×)
  12. dry with materialThe combined organic layers are dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto provide
  16. customTo separate the compounds the methyl esters
  17. customare formed
  18. customIn a flask are placed
  19. temperatureto reflux for 24 h
  20. concentrationThe solution is concentrated
  21. customchromatographed over silica gel (2% acetone-heptane)

Sources & evidence

ORD record
ord-c5670080c68f40679900c2dda31bc578
Source dataset
uspto-grants-2005_07
Patent number
US06919359B2

Reaction notes

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