Hydrochloric Acid → HCID 52914153, compound

HRID 540768Notes

Reaction equation

HRID 540768 reaction equation
C[Si](C)(C)[C:3]([F:6])([F:5])[F:4].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:27]([N:29]1[C:33]([O:34][C:35]2[CH:40]=[CH:39][C:38]([CH:41]=[O:42])=[CH:37][CH:36]=2)=[CH:32][C:31]([C:43]2[CH:44]=[C:45]([C:49]([NH:52][S:53]([CH2:56][C:57]([F:60])([F:59])[F:58])(=[O:55])=[O:54])([CH3:51])[CH3:50])[CH:46]=[CH:47][CH:48]=2)=[N:30]1)[CH3:28].Cl>O1CCCC1>[CH2:27]([N:29]1[C:33]([O:34][C:35]2[CH:36]=[CH:37][C:38]([CH:41]([OH:42])[C:3]([F:6])([F:5])[F:4])=[CH:39][CH:40]=2)=[CH:32][C:31]([C:43]2[CH:44]=[C:45]([C:49]([NH:52][S:53]([CH2:56][C:57]([F:60])([F:58])[F:59])(=[O:54])=[O:55])([CH3:51])[CH3:50])[CH:46]=[CH:47][CH:48]=2)=[N:30]1)[CH3:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 52913937HCID 52913937, compound

Product 1

HCID 52914153HCID 52914153, compoundYield 2.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Trimethyl(trifluoromethyl)silane (0.62 mL, 4.0 mmol, 1.2 equiv) and tetrabutylammonium fluoride (1.0 M in THF, 0.67 mL, 0.67 mmol, 0.20 equiv) were added sequentially to a solution of N-(1-{3-[1-ethyl-5-(4-formylphenoxy)-1H-pyrazol-3-yl]phenyl}-1-methylethyl)-2,2,2-trifluoroethanesulfonamide (1.65 g, 3.33 mmol, 1 equiv) in tetrahydrofuran (3.3 mL) at 0° C. The reaction mixture was stirred for 15 minutes at 0° C., and then was warmed to 22° C. After stirring for 2.5 hours, aqueous hydrochloric acid solution (2 N) was added and the reaction mixture was stirred for an additional 40 minutes. The crude product was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, and the washed solution was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated. The residue was purified by flash-column chromatography (hexanes, grading to 45% ethyl acetate-hexanes) to afford N-[1-(3-{1-ethyl-5-[4-(2,2,2-trifluoro-1-hydroxyethyl)phenoxy]-1H-pyrazol-3-yl}phenyl)-1-methylethyl]-2,2,2-trifluoroethanesulfonamide (43 mg, 2%). Calcd (M+1)+: 566.2. Found: 566.0.

Workup

  1. temperaturewas warmed to 22° C
  2. stirringAfter stirring for 2.5 hours
  3. stirringthe reaction mixture was stirred for an additional 40 minutes
  4. customThe crude product was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with saturated aqueous sodium chloride solution
  6. dry with materialthe washed solution was dried over sodium sulfate
  7. filtrationThe dried solution was filtered
  8. concentrationthe filtrate was concentrated
  9. customThe residue was purified by flash-column chromatography (hexanes, grading to 45% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-2c0b7c0e0fbc450088508e51c88f097f
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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