Allyl Alcohol → 5-(3-Oxo-propyl)-thiophene-2-carboxylic Acid Tert-butyl Ester
Reaction equation
[C:1]([O:5][C:6]([C:8]1[S:9][C:10](Br)=[CH:11][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([OH:17])[CH:15]=[CH2:16].C([O-])(O)=O.[Na+]>CN(C=O)C.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([C:8]1[S:9][C:10]([CH2:16][CH2:15][CH:14]=[O:17])=[CH:11][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 5
Conditions
- Temperature
- 65 °C
Procedure
To a solution of 5-bromo-thiophene-2-carboxylic acid tert-butyl ester prepared of the method of Preparation 4, Step A (0.50 g, 1.89 mmol) in 5 mL DMF was added allyl alcohol (0.51 mL, 7.57 mmol) followed by NaHCO3 (0.397 g, 4.72 mmol), tetrabutylammonium chloride (0.525 g, 1.89 mmol), and palladium acetate (0.021 g, 0.094 mmol). The reaction was placed in an oil bath heated to 65° C. and was heated to 90° C. for 2 h. The mixture was diluted with EtOAc and 25 mL water and the solids were removed by filtration through Celite®. The layers were separated, and the organic solution was washed with water (4×), dried over MgSO4 and concentrated to a dark yellow oil which was purified via medium pressure chromatography (7:1 hexanes:EtOAc) to afford the title compound (0.190 g). 1H NMR (400 MHz, CDCl3) δ 9.80 (s, 1H), 7.51 (d, 1H), 6.78 (d, 1H), 3.14 (t, 2H), 2.86 (t, 2H), 1.54 (s, 9H).
Workup
- customThe reaction was placed in an oil bath
- temperaturewas heated to 90° C. for 2 h
- customthe solids were removed by filtration through Celite®
- customThe layers were separated
- washthe organic solution was washed with water (4×)
- dry with materialdried over MgSO4
- concentrationconcentrated to a dark yellow oil which
- customwas purified via medium pressure chromatography (7:1 hexanes:EtOAc)
Sources & evidence
- ORD record
- ord-b674337d8f22422fa93e0db00f72226b
- Source dataset
- uspto-grants-2002_12
- Patent number
- US06498172B1
Reaction notes
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