Divinyl sulfone → THIOMORPHOLINE, 4-(2,6-DIFLUOROPHENYL)-, 1,1-DIOXIDE

HRID 395260Notes

Reaction equation

HRID 395260 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].ClC1C=CC=CC=1.[CH:12]([S:14]([CH:17]=[CH2:18])(=[O:16])=[O:15])=[CH2:13].[F:19][C:20]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:21]=1[NH2:22]>C(OCC)(=O)C>[F:19][C:20]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:21]=1[N:22]1[CH2:18][CH2:17][S:14](=[O:16])(=[O:15])[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 6496Divinyl sulfoneHCID 7964ChlorobenzeneHCID 796472,6-DifluoroanilineHCID 6451240Aluminum(III) Chloride

Product 1

HCID 9921212THIOMORPHOLINE, 4-(2,6-DIFLUOROPHENYL)-, 1,1-DIOXIDEYield 55.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Aluminum chloride (310 g, 2.3 mol) is added to chlorobenzene (2.5 L) to give a cloudy green suspension. Vinyl sulfone (230 mL, 2.3 mol) is added via a funnel. 2,6-Difluoroaniline (250 mL, 2.3 mol) is added a via funnel. The light brown solution is heated to 110° C. Upon completion, the heat is removed and the black solution is self-cooled to 70° C. The reaction mixture is quenched in methylene chloride (4 L) and ice water (5 L). The aqueous phase is extracted with methylene chloride. The combined organic layers are concentrated and added branched octane (3 L), and then cooled to 0° C. for 30 minutes. The solids are filtered and washed with branched octane (2×500 mL). The crude black solids are dissolved into methylene chloride (3 L) and then loaded onto a SiO2 plug (1.8 kg). The column is eluted with dichloromethane (16 L) until clear. The methylene chloride solution is concentrated to give light brown solids (387 g or 68% yield). The solids are dissolved in hot ethyl acetate (3 L) followed by the addition of hexanes (900 mL). The black solution is self-cooled to room temperature overnight. The light amber crystal needles are filtered and washed with hexanes (4×250 mL). The solids are dried in vacuo at 50° C. overnight to give 314 g of the title compound (55% recystallized yield 1st crop).

Workup

  1. customto give a cloudy green suspension
  2. customUpon completion, the heat is removed
  3. temperaturethe black solution is self-cooled to 70° C
  4. customThe reaction mixture is quenched in methylene chloride (4 L)
  5. extractionThe aqueous phase is extracted with methylene chloride
  6. concentrationThe combined organic layers are concentrated
  7. additionadded branched octane (3 L)
  8. temperaturecooled to 0° C. for 30 minutes
  9. filtrationThe solids are filtered
  10. washwashed with branched octane (2×500 mL)
  11. dissolutionThe crude black solids are dissolved into methylene chloride (3 L)
  12. washThe column is eluted with dichloromethane (16 L) until clear
  13. concentrationThe methylene chloride solution is concentrated
  14. customto give light brown solids (387 g or 68% yield)
  15. temperatureThe black solution is self-cooled to room temperature overnight
  16. filtrationThe light amber crystal needles are filtered
  17. washwashed with hexanes (4×250 mL)
  18. customThe solids are dried in vacuo at 50° C. overnight

Sources & evidence

ORD record
ord-af48db0e72784452a89862f5658dfa41
Source dataset
uspto-grants-2003_08
Patent number
US06605609B2

Reaction notes

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