Sodium Carbonate → ethyl 2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-2,5-dimethyl thiophen-3-yl]-2-oxoacetate

HRID 591021Notes

Reaction equation

HRID 591021 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[O:21][CH2:20][CH2:19][CH2:18]3)O1.Br[C:27]1[C:28]([C:34](=[O:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[C:29]([CH3:33])[S:30][C:31]=1[CH3:32]>O.CN(C)C=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[O:21]1[C:22]2[CH:23]=[CH:24][C:15]([C:27]3[C:28]([C:34](=[O:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[C:29]([CH3:33])[S:30][C:31]=3[CH3:32])=[CH:16][C:17]=2[CH2:18][CH2:19][CH2:20]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 438110342-(3,4-dihydro-2H-1-benzopyran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 70818387Ethyl (4-bromo-2,5-dimethyl-thiophen-3-yl)-oxo-acetate

Product 1

HCID 70855185ethyl 2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-2,5-dimethyl thiophen-3-yl]-2-oxoacetateYield 38%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Under a nitrogen atmosphere, sodium carbonate (78 mg, 0.7 mmol), palladium tetrakis(triphenylphosphine) (81 mg, 0.07 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (182 mg, 0.7 mmol) were added to a solution of ethyl (4-bromo-2,5-dimethyl-thiophen-3-yl)-oxo-acetate (17c) (200 mg, 0.69 mmol) in a mixture of water (3.5 mL) and N,N-dimethylformamide (11 mL). The mixture was heated at 110° C. for 1 hour. The mixture was then cooled at room temperature, concentrated in vacuo and water (30 mL) was added. The aqueous layer was extracted with ethyl acetate (2×30 mL). The organic layer was washed with brine (30 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 80/20) to afford the desired product (17d) as a white solid (90 mg, 0.26 mmol, 38%).

Workup

  1. temperatureThe mixture was then cooled at room temperature
  2. concentrationconcentrated in vacuo and water (30 mL)
  3. additionwas added
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×30 mL)
  5. washThe organic layer was washed with brine (30 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 80/20)

Sources & evidence

ORD record
ord-3bbb51847c4340ec983f0f88e6a00aaf
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

Loading…