4-Toluenesulfonyl chloride → HCID 67468537, compound

HRID 537222Notes

Reaction equation

HRID 537222 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:5]=[C:6]([C:10]2([F:25])[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1.C(N(C(C)C)CC)(C)C.[CH3:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([Cl:45])(=[O:44])=[O:43])=[CH:38][CH:37]=1>C(Cl)Cl>[ClH:45].[F:25][C:10]1([C:6]2[CH:5]=[C:4]([NH:3][S:42]([C:39]3[CH:40]=[CH:41][C:36]([CH3:35])=[CH:37][CH:38]=3)(=[O:44])=[O:43])[CH:9]=[CH:8][CH:7]=2)[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][O:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67467476HCID 67467476, compound

Product 1

HCID 67468537HCID 67468537, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-(3-aminophenyl)-1-(2-phenoxyethyl) 4-fluoropiperidine dihydrochloride (100 mg, 0.26 mmol) in methylene chloride (5 mL) was added diisopropylethylamine (118 mg, 0.91 mmol) and the mixture stirred at room temperature until a clear solution resulted. This solution was then cooled to 0° C. and 4-methyl-benzenesulfonyl chloride (58 mg, 0.28 mmol) was then added and the reaction stirred at 0° C. for 1 hour then room temperature for 3 hours. After this time the mixture was quenched by the addition of 25% ammonium chloride solution (10 mL). The organic layer was separated and the aqueous extracted with ethyl acetate (2×10 mL). The combined extracts were dried over magnesium sulfate and filtered and concentrated. The residue was re-dissolved in ethyl acetate (20 mL), washed with water (2×10 mL) and brine (10 mL), dried over magnesium sulfate and filtered. The filtrate was concentrated to a viscous yellow oil which was treated with 10% methanolic hydrogen chloride (10 mL) and re-concentrated. The residue was triturated with ethyl acetate (5 mL) and then dried under high vacuum to afford a 49% yield of the title compound as a light yellow solid.

Workup

  1. customresulted
  2. temperatureThis solution was then cooled to 0° C.
  3. stirringthe reaction stirred at 0° C. for 1 hour
  4. customAfter this time the mixture was quenched by the addition of 25% ammonium chloride solution (10 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous extracted with ethyl acetate (2×10 mL)
  7. dry with materialThe combined extracts were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was re-dissolved in ethyl acetate (20 mL)
  11. washwashed with water (2×10 mL) and brine (10 mL)
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationThe filtrate was concentrated to a viscous yellow oil which
  15. additionwas treated with 10% methanolic hydrogen chloride (10 mL)
  16. concentrationre-concentrated
  17. customThe residue was triturated with ethyl acetate (5 mL)
  18. customdried under high vacuum

Sources & evidence

ORD record
ord-27c49d92465c498fa4b7e637869378d5
Source dataset
uspto-grants-2014_10
Patent number
US08859777B2

Reaction notes

Loading…