3,3-Dimethyl-1-butyne → 5-(3,3-Dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid

HRID 579168Notes

Reaction equation

HRID 579168 reaction equation
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:48]1[S:52][C:51]([C:53]([OH:55])=[O:54])=[CH:50][CH:49]=1.[C:56]([C:60]#[CH:61])([CH3:59])([CH3:58])[CH3:57]>[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH3:57][C:56]([CH3:59])([CH3:58])[C:60]#[C:61][C:48]1[S:52][C:51]([C:53]([OH:55])=[O:54])=[CH:50][CH:49]=1

Participants

7

Reactant 3

HCID 135123,3-Dimethyl-1-butyneHCID 3491155-Bromothiophene-2-carboxylic acidHCID 634876Binap, (A+-)-

Product 1

HCID 581140725-(3,3-Dimethyl-but-1-ynyl)-thiophene-2-carboxylic acidYield 65%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A 350 mL heavy wall round bottom flask was charged with TEA (33.7 mL, 24 mmol, 5.0 equiv), BINAP (3.0 g, 4.83 mmol, 0.1 equiv), 5-bromo-thiophene-2-carboxylic acid (48.3 mmol, 1.0 equiv), CuI (0.184 g, 0.97 mmol, 0.02 equiv), Pd2dba3 (2.2 g, 2.4 mmol, 0.05 equiv) and DMF (40.0 mL). The flask was flushed with N2 and to the mixture was added t-butyl acetylene (15.8 g, 193 mmol, 4.0 equiv). The mixture was sealed and stirred at 70° C. for 48 hours. After cooled at room temperature, the reaction mixture was filtered and the filtrate was concentrated under vacuum. The residue was acidified with 3.0 N HCl until pH=4. The aqueous layer was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silical gel, EtOAc/heptane 5% to EtOAc/heptane 30% with 2% of AcOH to give product 6.5 g (yield 65%).

Workup

  1. customThe flask was flushed with N2 and to the mixture
  2. customThe mixture was sealed
  3. temperatureAfter cooled at room temperature
  4. filtrationthe reaction mixture was filtered
  5. concentrationthe filtrate was concentrated under vacuum
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was purified by silical gel, EtOAc/heptane 5% to EtOAc/heptane 30% with 2% of AcOH

Sources & evidence

ORD record
ord-9d9d397c21c64ccdad736cb9e4e80e24
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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