Trifluoromethanesulfonic acid → N-Methyldesloratadine

HRID 542762Notes

Reaction equation

HRID 542762 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][CH:6]([C:9]([C:11]2[C:16]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)=[CH:15][CH:14]=[CH:13][N:12]=2)=O)[CH2:5][CH2:4]1.FC(F)(F)S(O)(=O)=O>>[Cl:25][C:21]1[CH:22]=[CH:23][C:24]2[C:9](=[C:6]3[CH2:7][CH2:8][N:3]([CH3:2])[CH2:4][CH2:5]3)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:16]3[CH2:17][CH2:18][C:19]=2[CH:20]=1

Participants

3

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 13920590(3-(2-(3-Chlorophenyl)ethyl)-2-pyridinyl)(1-methyl-4-piperidinyl)methanone hydrochloride

Product 1

HCID 31843N-Methyldesloratadine

Procedure

A solution of 177 g (0.49 mole) of a product of Step D above in 480 mL (814.1 g, 5.31 mole) of trifluoromethanesulfonic acid at 90°-95° C. for 18 hours under nitrogen. Completeness of the reaction is determined by thin-layer chromatography. The cooled reaction is quenched with ice-water and the pH is adjusted to 6 with barium carbonate. The product is extracted into methylene chloride, which is concentrated under reduced pressure to about 1 liter and washed with water. The product is extracted into 1N hydrochloric acid, which is treated with 30 g of Darco, and filtered through celite. The pH of the filtrate is adjusted to 10 with 50% aqueous sodium hydroxide and the product is extracted into methylene chloride, which is removed under reduced pressure. The residue is dissolved in hot hexane, which is filtered to remove insolubles. The filtrate is concentrated to a residual beige powder. Yield: 126 g (HPLC purity 80%), 65% of theory.

Workup

  1. customThe cooled reaction
  2. customis quenched with ice-water
  3. extractionThe product is extracted into methylene chloride, which
  4. concentrationis concentrated under reduced pressure to about 1 liter
  5. washwashed with water
  6. extractionThe product is extracted into 1N hydrochloric acid, which
  7. additionis treated with 30 g of Darco
  8. filtrationfiltered through celite
  9. extractionthe product is extracted into methylene chloride, which
  10. customis removed under reduced pressure
  11. dissolutionThe residue is dissolved in hot hexane
  12. filtrationwhich is filtered
  13. customto remove insolubles
  14. concentrationThe filtrate is concentrated to a residual beige powder

Sources & evidence

ORD record
ord-5563e9701e70496b853870e221aa6204
Source dataset
uspto-grants-1987_04
Patent number
US04659716

Reaction notes

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