Ethanol → 2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-2,5-dimethyl thiophen-3-yl]-2-oxoacetic acid

HRID 591065Notes

Reaction equation

HRID 591065 reaction equation
Br[C:2]1[C:3]([C:9](=[O:15])[C:10]([O:12]CC)=[O:11])=[C:4]([CH3:8])[S:5][C:6]=1[CH3:7].C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:30]2[CH:31]=[C:32]3[C:37](=[CH:38][CH:39]=2)[O:36][CH2:35][CH2:34][CH2:33]3)O1.C(O)C>C1(C)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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].O>[O:36]1[C:37]2[CH:38]=[CH:39][C:30]([C:2]3[C:3]([C:9](=[O:15])[C:10]([OH:12])=[O:11])=[C:4]([CH3:8])[S:5][C:6]=3[CH3:7])=[CH:31][C:32]=2[CH2:33][CH2:34][CH2:35]1

Participants

8

Reactant 4

HCID 702EthanolHCID 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 708551932-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-2,5-dimethyl thiophen-3-yl]-2-oxoacetic acidYield 100%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

A solution of ethyl 2-(4-bromo-2,5-dimethylthiophen-3-yl)-2-oxoacetate (17c) (1.0 g, 3.43 mmol), sodium carbonate (1.46 g, 13.7 mmol), and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (1.16 g, 4.46 mmol) in a mixture of toluene (9 mL), ethanol (3 mL) and water (3.5 mL) was bubbled with nitrogen for 5 minutes. Palladium tetrakis(triphenylphosphine) (0.2 g, 0.17 mmol) was added and the reaction mixture was heated at 95° C. overnight. Water (5 mL) was added and the organic layer was extracted with 1N sodium hydroxide (5 mL). The combined aqueous layers were washed with ethyl acetate (10 mL), acidified with 1M hydrochloric acid until pH 2 and extracted with dichloromethane (2×10 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to provide the desired product (42a) (1.09 g, 3.43 mmol, 100%) which was used without further purification.

Workup

  1. customwas bubbled with nitrogen for 5 minutes
  2. extractionthe organic layer was extracted with 1N sodium hydroxide (5 mL)
  3. washThe combined aqueous layers were washed with ethyl acetate (10 mL)
  4. extractionextracted with dichloromethane (2×10 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b53374957af946358cd3c222fe4ba0bb
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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