4-Toluenesulfonyl chloride → 2,2-Difluoroethyl (4-methylphenyl)sulphonate

HRID 1371926Notes

Reaction equation

HRID 1371926 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[F:12][CH:13]([F:16])[CH2:14][OH:15]>N1C=CC=CC=1>[F:12][CH:13]([F:16])[CH2:14][O:15][S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)(=[O:9])=[O:8]

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 1361872,2-Difluoroethan-1-ol

Product 1

HCID 27823122,2-Difluoroethyl (4-methylphenyl)sulphonate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Combine p-toluenesulfonyl chloride (12.9 g, 67.4 mmol) in pyridine (15 mL) at room temperature and treat dropwise with 2,2-difluoroethanol (5.0 g, 60.9 mmol) via syringe. Stir the reaction mixture under nitrogen for 72 hours, partition between water (20 mL) and dichloromethane (20 mL). Separate the aqueous phase and extract with additional dichloromethane (2×40 mL). Combine the organic extracts and wash sequentially with 1N hydrochloric acid (2×50 mL), sodium bicarbonate (2×50 mL), and brine (2×50 mL). Dry the organic layer over sodium sulfate and concentrate in vacuo to give the title compound as a yellowish oil: 1H NMR (300 MHz, CDCl3): 7.82 (d, 2H, J=9.0 Hz), 7.40 (d, 2H, J=9.0 Hz), 5.92 (tt, 1H, J=55.0, 0.4 Hz), 4.19 (td, 2H, J=12.6, 4.0 Hz), 2.48 (s, 3H).

Workup

  1. custompartition between water (20 mL) and dichloromethane (20 mL)
  2. customSeparate the aqueous phase
  3. extractionextract with additional dichloromethane (2×40 mL)
  4. washCombine the organic extracts and wash sequentially with 1N hydrochloric acid (2×50 mL), sodium bicarbonate (2×50 mL), and brine (2×50 mL)
  5. dry with materialDry the organic layer over sodium sulfate
  6. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-422655b69cd64976a2b95cb8bc6df1c7
Source dataset
uspto-grants-2007_01
Patent number
US07157488B2

Reaction notes

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