Ethanol → Ethyl 2-(tert-butoxy)-2-(3,5-diphenylthiophen-2-yl)acetate

HRID 590976Notes

Reaction equation

HRID 590976 reaction equation
[C:1]([O:5][CH:6]([C:12]1[S:13][C:14](Br)=[CH:15][C:16]=1Br)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[C:19]1(B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:34](O)[CH3:35]>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>[C:1]([O:5][CH:6]([C:12]1[S:13][C:14]([C:35]2[CH:34]=[CH:16][CH:12]=[CH:6][CH:7]=2)=[CH:15][C:16]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 70819068Ethyl 2-(tert-butoxy)-2-(3,5-dibromothiophen-2-yl)acetate

Product 1

HCID 70818072Ethyl 2-(tert-butoxy)-2-(3,5-diphenylthiophen-2-yl)acetateYield 51%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
95 °C

Procedure

A solution of ethyl 2-(tert-butoxy)-2-(3,5-dibromothiophen-2-yl)acetate (100 mg, 0.25 mmol), phenylboronic acid (36 mg, 0.30 mmol) and sodium carbonate (106 mg, 1.00 mmol) in a mixture of toluene (1.26 mL), ethanol (0.6 mL) and water (0.5 mL) was bubbled with nitrogen for 5 minutes. Palladium tetrakis(triphenylphosphine) (14 mg, 0.01 mmol) was added and the reaction mixture was heated a 95° C. overnight. After cooling to room temperature, water (2 mL) was added. The aqueous layer was extracted with toluene (2×8 mL). The organic layers were washed with brine (5 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 80/20) to provide ethyl 2-(tert-butoxy)-2-(3,5-diphenylthiophen-2-yl)acetate (50 mg, 0.13 mmol, 51%).

Workup

  1. customwas bubbled with nitrogen for 5 minutes
  2. temperatureAfter cooling to room temperature
  3. extractionThe aqueous layer was extracted with toluene (2×8 mL)
  4. washThe organic layers were washed with brine (5 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 80/20)

Sources & evidence

ORD record
ord-e1e5cb0b2cac407eaaddc8be046ea0a0
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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