Methanesulfonic Acid → HCID 21072792, compound

HRID 1372888Notes

Reaction equation

HRID 1372888 reaction equation
C([NH:5][C:6](=[O:27])[C:7]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[CH3:20])=[CH:11][C:10]([N:21]2[CH2:26][CH2:25][S:24][CH2:23][CH2:22]2)=[N:9][CH:8]=1)(C)(C)C.CS(O)(=O)=O>C1(C)C=CC=CC=1>[F:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]2[C:7]([C:6]([NH2:5])=[O:27])=[CH:8][N:9]=[C:10]([N:21]3[CH2:26][CH2:25][S:24][CH2:23][CH2:22]3)[CH:11]=2)=[C:14]([CH3:20])[CH:15]=1

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 21072795HCID 21072795, compound

Product 1

HCID 21072792HCID 21072792, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4-(4-Fluoro-2-methyl-phenyl)-6-thiomorpholin-4-yl-nicotinamide can be produced by suspending N-tert-Butyl-4-(4-fluoro-2-methyl-phenyl)-6-thiomorpholin-4-yl-nicotinamide in toluene. The suspension is heated with the dropwise addition of methanesulfonic acid to provide an emulsion, which is then stirred and cooled to room temperature. The phases are separated and the organic phase washed with deionized water. The combined aqueous phases are cooled to about 0° C., followed by the slow addition of 28% aqueous sodium hydroxide to increase the pH to about 12.5. The suspension obtained then can be extracted with dichloromethane. The combined organic extracts are dried and concentrated in a rotary evaporator. Propyl acetate is then added, and the solution concentrated in a rotary evaporator. A second portion of propyl acetate is added, and the solution concentrated to form a suspension. N-hexane is added to the suspension, followed by stirring. The resulting precipitate is filtered off, washed with n-hexane:propyl acetate 9:1, and dried in a vacuum oven to yield 4-(4-fluoro-2-methyl-phenyl)-6-thiomorpholin-4-yl-nicotinamide as a light yellow powder.

Workup

  1. customto provide an emulsion, which
  2. customThe phases are separated
  3. washthe organic phase washed with deionized water
  4. temperatureThe combined aqueous phases are cooled to about 0° C.
  5. additionfollowed by the slow addition of 28% aqueous sodium hydroxide
  6. temperatureto increase the pH to about 12.5
  7. customThe suspension obtained
  8. extractioncan be extracted with dichloromethane
  9. customThe combined organic extracts are dried
  10. concentrationconcentrated in a rotary evaporator
  11. additionPropyl acetate is then added
  12. concentrationthe solution concentrated in a rotary evaporator
  13. additionA second portion of propyl acetate is added
  14. concentrationthe solution concentrated
  15. customto form a suspension
  16. stirringby stirring
  17. filtrationThe resulting precipitate is filtered off
  18. washwashed with n-hexane:propyl acetate 9:1
  19. customdried in a vacuum oven

Sources & evidence

ORD record
ord-bf53dd08ae4e4386a546821a72c76e9c
Source dataset
uspto-grants-2007_01
Patent number
US07160881B2

Reaction notes

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