Ethyl Acetate → n-[3-Tert-butyl-1-(4,4,4-trifluorobutyl)-1h-pyrazol-5-yl]-2-fluoro-5-(trifluoromethyl)benzamide

HRID 536760Notes

Reaction equation

HRID 536760 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([CH2:11][CH2:12][CH2:13][C:14]([F:17])([F:16])[F:15])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:18][C:19]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:20]=1[C:21](Cl)=[O:22].CCOC(C)=O>C1COCC1.CCN(CC)CC.CO>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:21](=[O:22])[C:20]2[CH:24]=[C:25]([C:28]([F:29])([F:30])[F:31])[CH:26]=[CH:27][C:19]=2[F:18])[N:7]([CH2:11][CH2:12][CH2:13][C:14]([F:16])([F:17])[F:15])[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 8857Ethyl Acetate2×HCID 27348802-Fluoro-5-(trifluoromethyl)benzoyl ChlorideHCID 666432243-Tert-butyl-1-(4,4,4-trifluorobutyl)-1h-pyrazol-5-amine

Product 1

HCID 87087570n-[3-Tert-butyl-1-(4,4,4-trifluorobutyl)-1h-pyrazol-5-yl]-2-fluoro-5-(trifluoromethyl)benzamideYield 80.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Procedure

To a solution of Example 135B (2.0 g, 8.1 mmol) and Et3N (3.4 mL, 24.3 mmol) in THF (40 mL) was added 2-fluoro-5-(trifluoromethyl)benzoyl chloride (1.2 mL, 8.1 mmol). The mixture was allowed to stir at ambient temperature for 3 h then partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted EtOAc (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (2.9 g, 6.5 mmol, 80% yield). MS (ESI+) m/z 440 (M+H)+.

Workup

  1. customthen partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL)
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted EtOAc (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (SiO2, 50% hexanes/EtOAc

Sources & evidence

ORD record
ord-f7a5500fe89048ac8473c21554ef23c5
Source dataset
uspto-grants-2014_10
Patent number
US08859596B2

Reaction notes

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