Methanesulfonic Acid → HCID 21072792, compound

HRID 1372892Notes

Reaction equation

HRID 1372892 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, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

9.7 g (25 mmol) N-tert-Butyl-4-(4-fluoro-2-methyl-phenyl)-6-thiomorpholin-4-yl-nicotinamide suspended in 48.5 ml toluene was heated to 95° C. and 24.0 g methanesulfonic acid was added dropwise giving an emulsion, which was stirred at 100° C. for two hours. After cooling to room temperature, the phases were separated and the organic phase was washed with deionized water. The combined aqueous phases were cooled to 0° C. and 28% aqueous sodium hydroxide was slowly added to increase the pH to ca. 12.5. The suspension obtained was extracted with dichloromethane. The combined organic extracts were dried and concentrated in a rotary evaporator. 100 ml Propyl acetate was added and the solution was concentrated in a rotary evaporator. A second portion of 100 ml propyl acetate was added and the solution was concentrated to ca. 23 g, forming a suspension to which 8.3 ml n-hexane was added. The suspension was stirred at 0° C. for one hour. The precipitate was filtered off, washed with n-hexane/propyl acetate 9:1 and dried in a vacuum oven to yield 8.0 g (97 %) 4-(4-fluoro-2-methyl-phenyl)-6-thiomorpholin-4-yl-nicotinamide as a light yellow powder of m.p.=198–202° C.

Workup

  1. customgiving an emulsion, which
  2. temperatureAfter cooling to room temperature
  3. customthe phases were separated
  4. washthe organic phase was washed with deionized water
  5. temperatureThe combined aqueous phases were cooled to 0° C.
  6. addition28% aqueous sodium hydroxide was slowly added
  7. temperatureto increase the pH to ca. 12.5
  8. customThe suspension obtained
  9. extractionwas extracted with dichloromethane
  10. customThe combined organic extracts were dried
  11. concentrationconcentrated in a rotary evaporator
  12. addition100 ml Propyl acetate was added
  13. concentrationthe solution was concentrated in a rotary evaporator
  14. additionA second portion of 100 ml propyl acetate was added
  15. concentrationthe solution was concentrated to ca. 23 g
  16. customforming a suspension to which 8.3 ml n-hexane
  17. additionwas added
  18. stirringThe suspension was stirred at 0° C. for one hour
  19. filtrationThe precipitate was filtered off
  20. washwashed with n-hexane/propyl acetate 9:1
  21. customdried in a vacuum oven

Sources & evidence

ORD record
ord-f517402f40ec4094a938eb6e24410239
Source dataset
uspto-grants-2007_01
Patent number
US07160881B2

Reaction notes

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