4-Toluenesulfonyl chloride → HCID 59557759, compound

HRID 2174339Notes

Reaction equation

HRID 2174339 reaction equation
[OH-].[Na+].[F:3][CH:4]([F:10])[CH2:5][O:6][CH2:7][CH2:8][OH:9].[S:11](Cl)([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12]>C1COCC1.O>[CH3:18][C:17]1[CH:19]=[CH:20][C:14]([S:11]([O:9][CH2:8][CH2:7][O:6][CH2:5][CH:4]([F:10])[F:3])(=[O:13])=[O:12])=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 534127602-(2,2-Difluoroethoxy)ethan-1-ol

Product 1

HCID 59557759HCID 59557759, compoundYield 112.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (0° C.) solution of 4.6 N sodium hydroxide (20.6 mL) was slowly added 2-(2,2-difluoroethoxy)ethanol (4 g, 31.7 mmol) in THF (10 mL) at a rate that maintained the temperature below 5° C. The mixture was stirred for 10 minutes, and TsCl (6.1 g, 32 mmol) in THF (10.6 mL) was slowly added at a rate that maintained the temperature below 5° C. The mixture was stirred for 30 minutes below 5° C., and then diluted with water. The aqueous layer was extracted with EtOAc (2×20 mL), and the combined organic layers were washed with aqueous NH4Cl (30 mL), then with brine (30 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure gave the crude product, which was purified by silica column chromatography (elution with PE:EtOAc=4:1) to give the title compound (10 g, yield 81.9%). 1H-NMR (CDCl3, 400 MHz): δ 7.78 (d, J=8.4 Hz, 2H), 7.33 (d, J=8 Hz, 2H), 5.77 (ttt, J=4, 5.52 Hz, 1H), 4.16 (t, J=4.4 Hz, 2H), 3.74 (t, J=4.8 Hz, 2H), 3.62 (dt, J=4, 14 Hz, 2H), 2.44 (s, 3H).

Workup

  1. temperaturemaintained the temperature below 5° C
  2. temperaturethat maintained the temperature below 5° C
  3. stirringThe mixture was stirred for 30 minutes below 5° C.
  4. extractionThe aqueous layer was extracted with EtOAc (2×20 mL)
  5. washthe combined organic layers were washed with aqueous NH4Cl (30 mL)
  6. dry with materialwith brine (30 mL), and dried over anhydrous sodium sulfate
  7. concentrationConcentration under reduced pressure
  8. customgave the crude product, which
  9. customwas purified by silica column chromatography (elution with PE:EtOAc=4:1)

Sources & evidence

ORD record
ord-6a072c9c26ae4742833018f283c7de4c
Source dataset
uspto-grants-2015_06
Patent number
US09061060B2

Reaction notes

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