3-Fluorophenol → 4-(3-Fluoro-phenoxy)-thiophen-2-yl-[1,3]dioxolane

HRID 2080072Notes

Reaction equation

HRID 2080072 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]2[O:11][CH2:10][CH2:9][O:8]2)[S:5][CH:6]=1.[F:12][C:13]1[CH:14]=[C:15]([OH:19])[CH:16]=[CH:17][CH:18]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.[Cu]Cl.C(OCC)(=O)C.CCCCCC>[F:12][C:13]1[CH:14]=[C:15]([CH:16]=[CH:17][CH:18]=1)[O:19][C:2]1[CH:3]=[C:4]([CH:7]2[O:11][CH2:10][CH2:9][O:8]2)[S:5][CH:6]=1

Participants

9

Reactant 4

HCID 97433-FluorophenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedione2×HCID 38572552-(4-Bromothiophen-2-yl)-1,3-dioxolane

Product 1

HCID 231305304-(3-Fluoro-phenoxy)-thiophen-2-yl-[1,3]dioxolaneYield 24.4%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

2-(4-Bromo-thiophen-2-yl)-[1,3]dioxolane (1.0 g, 4.3 mmol), 3-fluorophenol (0.95 g, 8.6 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.078 g, 0.43 mmol), copper(I) chloride (0.21 g, 2.7 mmol) and cesium carbonate (2.8 g, 8.6 mmol) were suspended in N-methylpyrrolidone (10 mL) under a nitrogen stream, and the mixture was stirred for 4.5 hours at 120° C. To this suspension was added 2,2,6,6-tetramethyl-3,5-heptanedione (0.12 g, 0.65 mmol), and the solution was further stirred for 8 hours at 140° C. The reaction mixture was filtered through Celite pad, then, water and ethyl acetate were added for partitioning, and the organic layer was washed with water twice. NH silica gel was added to the organic layer, the solvent was evaporated in vacuo for adsorption to NH silica gel, purification was carried out by NH silica gel column chromatography (hexane, then hexane:ethyl acetate=30:1), and the title compound (280 mg, 1.05 mmol, 24.4%) was obtained as a colorless oil.

Workup

  1. stirringthe solution was further stirred for 8 hours at 140° C
  2. filtrationThe reaction mixture was filtered through Celite pad
  3. additionwater and ethyl acetate were added
  4. customfor partitioning
  5. washthe organic layer was washed with water twice
  6. additionNH silica gel was added to the organic layer
  7. customthe solvent was evaporated in vacuo for adsorption to NH silica gel, purification

Sources & evidence

ORD record
ord-5dd2f031dc8d49ec98c9c4095b7f81f6
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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