2,6-Lutidine → HCID 57383517, compound

HRID 854430Notes

Reaction equation

HRID 854430 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]([S:13]([C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[NH:10][CH:11]=O.P(Cl)(Cl)(Cl)=O.N1C(C)=CC=CC=1C>C1COCC1>[C:19]1([CH3:22])[CH:18]=[CH:17][C:16]([S:13]([CH:9]([N+:10]#[C-:11])[C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])(=[O:15])=[O:14])=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 85947460HCID 85947460, compound

Product 1

HCID 57383517HCID 57383517, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of N-[(2,6-Difluoro-phenyl)-(toluene-4-sulfonyl)-methyl]-formamide (2.07 g, 6.36 mmol) and THF (15 mL) is added phosphorous oxychloride (POCl3) (1.19 mL, 12.7 mmol) over a period of 5 minutes, and the resulting mixture stirred at room temperature for 10 minutes. The reaction is then cooled to 4° C. using an ice/water bath and 2,6-lutidine (4.45 mL, 38.2 mmol) is added over 30 minutes, maintaining the temperature less than 12° C. The cooling bath is removed and the mixture stirred at room temperature for 18 hours. The reaction mixture is poured into a stirred, ice water cooled solution of ice and saturated aqueous sodium bicarbonate (NaHCO3). The mixture is extracted with ethyl acetate (2×). The combined organic extracts are washed with 1N aqueous hydrochloric acid (30.0 mL), saturated aqueous sodium bicarbonate (NaHCO3) (30.0 mL), brine (30.0 mL) and dried (MgSO4). The solvents are removed in vacuo, and isopropanol (18.0 mL) is added to the residual brownish solid. The resulting slurry is stirred at room temperature for 2 hours, then water is added and the slurry stirred for an additional 30 minutes at room temperature. The slurry is filtered, the cake washed with 2:1 isopropanol-water (2×) and dried in a vacuum-oven (30° C.) for 48 hours. The title compound may be obtained as a tan solid (1.33 g, 68%).

Workup

  1. temperatureThe reaction is then cooled to 4° C.
  2. temperaturemaintaining the temperature less than 12° C
  3. customThe cooling bath is removed
  4. stirringthe mixture stirred at room temperature for 18 hours
  5. additionThe reaction mixture is poured into a stirred, ice water cooled solution of ice and saturated aqueous sodium bicarbonate (NaHCO3)
  6. extractionThe mixture is extracted with ethyl acetate (2×)
  7. washThe combined organic extracts are washed with 1N aqueous hydrochloric acid (30.0 mL), saturated aqueous sodium bicarbonate (NaHCO3) (30.0 mL), brine (30.0 mL)
  8. dry with materialdried (MgSO4)
  9. customThe solvents are removed in vacuo, and isopropanol (18.0 mL)
  10. additionis added to the residual brownish solid
  11. stirringThe resulting slurry is stirred at room temperature for 2 hours
  12. additionwater is added
  13. stirringthe slurry stirred for an additional 30 minutes at room temperature
  14. filtrationThe slurry is filtered
  15. washthe cake washed with 2:1 isopropanol-water (2×)
  16. customdried in a vacuum-oven (30° C.) for 48 hours

Sources & evidence

ORD record
ord-20bda477e42145a181e087160a734080
Source dataset
uspto-grants-2007_08
Patent number
US07259171B2

Reaction notes

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