Sodium Carbonate → 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxothiomorpholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide

HRID 1372895Notes

Reaction equation

HRID 1372895 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C:13]([CH3:39])([CH3:38])[C:14]([N:16]([CH3:37])[C:17]2[CH:18]=[N:19][C:20]([N:31]3[CH2:36][CH2:35]S[CH2:33][CH2:32]3)=[CH:21][C:22]=2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=2[CH3:30])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O[O:43][S:44]([O-:46])=O.[K+].S([O-])(O)=O.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CO>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C:13]([CH3:39])([CH3:38])[C:14]([N:16]([C:17]2[CH:18]=[N:19][C:20]([N:31]3[CH2:32][CH2:33][S:44](=[O:46])(=[O:43])[CH2:35][CH2:36]3)=[CH:21][C:22]=2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=2[CH3:30])[CH3:37])=[O:15])[CH:4]=[C:3]([C:2]([F:40])([F:41])[F:1])[CH:8]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 22591451HCID 22591451, compoundHCID 23665763Sodium BisulfiteHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 98307032-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxothiomorpholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramideYield 83.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5.0 g (8.3 mmol) 2-(3,5-Bis-trifluoromethyl-phenyl)-N-methyl-N-[4-(4-fluoro-2-methyl-phenyl)-6-thiomorpholin-4-yl-pyridin-3-yl]-isobutyramide was suspended in 50 ml methanol and treated at room temperature with 6.4 g (10.4 mmol) oxone™. The suspension was stirred for 16 hours at room temperature, cooled to 0° C. and 3.4 ml (16.7 mmol) sodium hydrogen sulfite solution was added dropwise. The stirring was pursued for 30 minutes at room temperature and the pH adjusted to ca. 8.5 with saturated aqueous sodium carbonate. The methanol was evaporated under reduced pressure and the residue was extracted with dichloromethane. The organic phase was washed with half-saturated aqueous sodium chloride. The solvent was exchanged under reduced pressure in a rotary evaporator with 60 ml isopropanol and the volume reduced to ca. 40 ml. The solution was cooled to room temperature under stirring within 2 hours and stirred further for 1 hour. The precipitate formed was filtered off, washed with 5 ml isopropanol and dried under high vacuum to yield 4.4 g (83.5%) 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxothiomorpholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide as a white powder of m.p.=135–138° C.

Workup

  1. temperaturecooled to 0° C.
  2. waitThe stirring was pursued for 30 minutes at room temperature
  3. customThe methanol was evaporated under reduced pressure
  4. extractionthe residue was extracted with dichloromethane
  5. washThe organic phase was washed with half-saturated aqueous sodium chloride
  6. customThe solvent was exchanged under reduced pressure in a rotary evaporator with 60 ml isopropanol
  7. temperatureThe solution was cooled to room temperature
  8. stirringunder stirring within 2 hours
  9. stirringstirred further for 1 hour
  10. customThe precipitate formed
  11. filtrationwas filtered off
  12. washwashed with 5 ml isopropanol
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-d23acbce352344ca817e24063a52b9d4
Source dataset
uspto-grants-2007_01
Patent number
US07160881B2

Reaction notes

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