Sodium Iodide → 5-(2-{4-[5-(4-Chloro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide hydrochloride

HRID 2288995Notes

Reaction equation

HRID 2288995 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:19][C:18]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[N:17][C:16]=2[CH2:26][O:27][CH2:28][C:29]([F:32])([F:31])[F:30])=[CH:11][CH:10]=1.Cl[CH2:34][CH2:35][C:36]1[CH:37]=[CH:38][C:39]([O:46][CH3:47])=[C:40]([S:42]([NH2:45])(=[O:44])=[O:43])[CH:41]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>C(=O)([O-])[O-].[Na+].[Na+]>[ClH:8].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:19][C:18]([CH:20]3[CH2:25][CH2:24][N:23]([CH2:34][CH2:35][C:36]4[CH:37]=[CH:38][C:39]([O:46][CH3:47])=[C:40]([S:42]([NH2:45])(=[O:43])=[O:44])[CH:41]=4)[CH2:22][CH2:21]3)=[N:17][C:16]=2[CH2:26][O:27][CH2:28][C:29]([F:30])([F:31])[F:32])=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 187004174-[5-(4-Chlorophenyl)-4-(2,2,2-trifluoroethoxymethyl)-oxazol-2-yl]piperidine trifluoroacetateHCID 187004435-(2-Chloroethyl)-2-methoxy-benzenesulfonamide

Product 1

HCID 187004035-(2-{4-[5-(4-Chloro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide hydrochloride

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent

Conditions

Temperature
100 °C

Procedure

4-[5-(4-chloro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2yl]-piperidine trifluoroacetate (1.1 g, 2.05 mmol), prepared as in Intermediate 12, is taken up in saturated sodium carbonate and extracted with ethyl acetate. The organics are dried over magnesium sulfate and concentrated under reduced pressure. The residue is taken up in 1,4-dioxane (70 ml) and stirred. To this solution is added 5-(2-chloro-ethyl)-2-methoxy-benzenesulfonamide (0.77 g, 3.07 mmol), prepared as in Intermediate 13, sodium iodide (0.61 g, 4.10 mmol), and diisopropyl ethyl amine (0.71 ml, 4.10 mmol) and the mixture is heated to 100° C. for 16 h. After cooling to room temperature, the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using a gradient of (1:9) methanol/ethyl acetate to (1:9) methanol/ethyl acetate with 1% ammonium hydroxide as eluant. (Rf =0.13 in (1:9) methanol/ethyl acetate, visualization by UV and iodoplatinate solution) The product is further purified by reverse phase HPLC using acetonitrile/water (15% to 80% gradient over 30 min) as eluant. The fractions collected are washed with saturated sodium carbonate and extracted with ethyl acetate. The organics are dried over magnesium sulfate and the solvent removed under reduced pressure. The residue is taken up in minimal ethyl acetate (5 ml) and 1M hydrochloric acid in ether is added dropwise until a precipitate formed. The solvent is removed under reduced pressure to yield the title compound.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organics are dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionTo this solution is added
  5. temperatureAfter cooling to room temperature
  6. customthe solvent is removed under reduced pressure
  7. customThe residue is purified by silica gel chromatography
  8. custom(Rf =0.13 in (1:9) methanol/ethyl acetate, visualization by UV and iodoplatinate solution) The product is further purified by reverse phase
  9. customacetonitrile/water (15% to 80% gradient over 30 min)
  10. customThe fractions collected
  11. washare washed with saturated sodium carbonate
  12. extractionextracted with ethyl acetate
  13. dry with materialThe organics are dried over magnesium sulfate
  14. customthe solvent removed under reduced pressure
  15. addition1M hydrochloric acid in ether is added dropwise until a precipitate
  16. customformed
  17. customThe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-7ff91188cf09401fb408a1ae14972da6
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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