Hydrochloric Acid → Ethyl 4-(4'-fluorobiphenyl-4-yl)-2-(methylsulfonyl)butanoate

HRID 533573Notes

Reaction equation

HRID 533573 reaction equation
[CH2:1]([O:3][C:4](=[O:10])[CH2:5][S:6]([CH3:9])(=[O:8])=[O:7])[CH3:2].[H-].[Na+].[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH2:27]I)=[CH:22][CH:21]=2)=[CH:16][CH:15]=1.Cl>CN(C=O)C>[F:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH:5]([S:6]([CH3:9])(=[O:8])=[O:7])[C:4]([O:3][CH2:1][CH3:2])=[O:10])=[CH:22][CH:21]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 78201Ethyl methanesulfonylacetateHCID 665779344-Fluoro-4'-(2-iodoethyl)biphenyl

Product 1

HCID 66577988Ethyl 4-(4'-fluorobiphenyl-4-yl)-2-(methylsulfonyl)butanoateYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of ethyl(methylsulphonyl)acetate (330 mg, 1.99 mmol) in 4 mL of DMF was treated with sodium hydride (88 mg, 60% dispersion in mineral oil, 2.19 mmol), until effervescence ceased in an ice bath under nitrogen. To this was added 4-fluoro-4′-(2-iodoethyl)biphenyl (650 mg, 1.99 mmol) as a solid and the residual material was dissolved by the addition of DMF (2 mL). The mixture was warmed to room temperature, then heated at 50° C. for 2 hours. The mixture was then cooled to room temperature, poured into 60 mL of 0.5N aqueous HCl and extracted 2×60 mL with ethyl acetate. The organic phase was dried over sodium sulfate filtered and concentrated in vacuo to yield a light yellow oil with some white solid particulates. The crude yield was 840 mg. The material was purified by flash chromatography on a 40 mm flash column using 120 g silica gel eluting with 0-50% ethyl acetate/heptane. This afforded the title compound as an oil (510 mg, 70.2%). MS (LC/MS) m/z 365.2 (M+1).

Workup

  1. customceased in an ice bath under nitrogen
  2. temperatureheated at 50° C. for 2 hours
  3. temperatureThe mixture was then cooled to room temperature
  4. extractionextracted 2×60 mL with ethyl acetate
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto yield a light yellow oil with some white solid particulates
  9. customThe material was purified by flash chromatography on a 40 mm flash column

Sources & evidence

ORD record
ord-2513a9d474d342989b21e488cb3e30e6
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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