Water → {4-[4-(2-Chloro-phenylsulfanyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester

HRID 1468356Notes

Reaction equation

HRID 1468356 reaction equation
[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13](B2OC(C)(C)C(C)(C)O2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:25])[CH:11]=2)[CH:6]=1.Br[C:28]1[CH:33]=[CH:32][C:31]([S:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[Cl:41])=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].O>C(COC)OC.[Pd].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>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:28]2[CH:29]=[CH:30][C:31]([S:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[Cl:41])=[CH:32][CH:33]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:25])[CH:11]=2)[CH:6]=1

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 197368221-Bromo-4-(2-chlorophenylsulfanyl)-benzeneHCID 59350821[6-Fluoro-3-methyl-4-(4,4,5,5-tetra methyl-[1,3,2]-dioxaborolan-2-yl)-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 86694949{4-[4-(2-Chloro-phenylsulfanyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl esterYield 28%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A stirred solution of [6-fluoro-3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-naphthalen-2-yl]-acetic acid methyl ester (0.2 g, 0.56 mmol) in dimethoxyethane (5 mL) was purged with argon for 5 minutes at room temperature. Tetrakis(triphenylphosphine)-palladium(0) (0.032 g, 0.028 mmol), impure 1-bromo-4-(2-chlorophenylsulfanyl)-benzene (0.334 g) and 1.0 M aqueous sodium bicarbonate (5 mL, 5 mmol) were added simultaneously to the reaction mixture under argon. The reaction mixture was refluxed for 2 hours and then cooled to room temperature. Water was added and the resulting mixture was extracted twice with ethyl acetate. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product, which was purified using flash chromatography (0-3% ethyl acetate in hexanes) to give {4-[4-(2-chloro-phenylsulfanyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.07 g, 28%) as a solid.

Workup

  1. temperatureThe reaction mixture was refluxed for 2 hours
  2. extractionthe resulting mixture was extracted twice with ethyl acetate
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give a crude product, which
  7. customwas purified

Sources & evidence

ORD record
ord-c4d3ea3d56224f4b8cc03e063b904f7b
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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