Methyl triflate → HCID 178480273, compound

HRID 536761Notes

Reaction equation

HRID 536761 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:23])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=2[F:22])[N:7]([CH2:24][CH2:25][CH2:26][C:27]([F:30])([F:29])[F:28])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].F[C:32](F)(F)S(OC)(=O)=O.[NH4+].[OH-]>C1(C)C=CC=CC=1.O.CC(C)=O>[C:1]([C:5]1[N:6]([CH3:32])[N:7]([CH2:24][CH2:25][CH2:26][C:27]([F:30])([F:29])[F:28])/[C:8](=[N:10]/[C:11](=[O:23])[C:12]2[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[CH:14][C:13]=2[F:22])/[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 9526Methyl triflateHCID 14923Ammonium HydroxideHCID 87087570n-[3-Tert-butyl-1-(4,4,4-trifluorobutyl)-1h-pyrazol-5-yl]-2-fluoro-5-(trifluoromethyl)benzamide

Product 1

HCID 178480273HCID 178480273, compoundYield 74.4%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of Example 135C (1.7 g, 3.9 mmol) in toluene (15 mL) was added methyl trifluoromethanesulfonate (0.64 mL, 5.8 mmol). The mixture was warmed to 100° C. and stirred for 20 hours, cooled to ambient temperature and diluted with water (20 mL) and acetone (50 mL). This solution was allowed to stir for 30 minutes then concentrated NH4OH (10 mL) was added. The mixture was stirred for 30 minutes then partially concentrated under reduced pressure. The mixture was diluted with EtOAc (30 mL) and brine (10 mL) and the layers were separated. The aqueous phase was extracted with EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 80% hexanes/EtOAc to 100% EtOAc to 10% MeOH in EtOAc) afforded the title compound (1.3 g, 2.9 mmol, 74% yield). MS (ESI+) m/z 454 (M+H)+.

Workup

  1. temperaturecooled to ambient temperature
  2. stirringto stir for 30 minutes
  3. stirringThe mixture was stirred for 30 minutes
  4. concentrationthen partially concentrated under reduced pressure
  5. additionThe mixture was diluted with EtOAc (30 mL) and brine (10 mL)
  6. customthe layers were separated
  7. extractionThe aqueous phase was extracted with EtOAc (3×5 mL)
  8. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by column chromatography (SiO2, 80% hexanes/EtOAc to 100% EtOAc to 10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-5fcf102ff54c4ff1b99fc8c778dc19aa
Source dataset
uspto-grants-2014_10
Patent number
US08859596B2

Reaction notes

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