Ethyl Acetate → HCID 90405103, compound

HRID 1772524Notes

Reaction equation

HRID 1772524 reaction equation
[H-].[Na+].[F:3][C:4]([F:28])([F:27])[O:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH:16]=[N:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23](=O)[CH2:24][CH3:25])=[CH:19][CH:18]=3)=[N:13]2)=[CH:8][CH:7]=1.[C:29]([O:32][CH2:33][CH3:34])(=[O:31])[CH3:30]>O.[Pd]>[F:28][C:4]([F:3])([F:27])[O:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH:16]=[N:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH2:24][CH3:25])[CH2:30][C:29]([O:32][CH2:33][CH3:34])=[O:31])=[CH:19][CH:18]=3)=[N:13]2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 90404626HCID 90404626, compound

Product 1

HCID 90405103HCID 90405103, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

Sodium hydride (60% immersion in oil, 0.32 g, 7.9 mmol) was weighed into an oven-dried three neck round bottomed flask. The flask was placed under nitrogen and tetrahydrofuran (44 mL) was added. The stirring mixture was placed in an ice bath. Triethylphosphonoacetate (1.4 mL, 6.9 mmol) was added and the mixture was stirred for 2 hours. Added 1-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-1-one (CA7) (2.4 g, 6.5 mmol) as a solid and warmed to room temperature overnight. The reaction was diluted with water and extracted with ethyl acetate/hexanes (1:1, 2×). The organic layers were dried over sodium sulfate, filtered, and concentrated. To the crude residue was added palladium on carbon (10 wt %, 0.70 g, 0.66 mmol) and dissolved in ethyl acetate (20 mL). The reaction was stirred under hydrogen by balloon overnight. The reaction mixture was filtered through Celite® and concentrated to give the title compound as a brown liquid (2.7 g, 90%): 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J=0.6 Hz, 1H), 8.11 (dd, J=8.1, 6.0 Hz, 2H), 7.83-7.76 (m, 2H), 7.38 (dq, J=7.9, 1.0 Hz, 2H), 7.35-7.27 (m, 2H), 4.24-4.14 (m, 1H), 4.04 (qd, J=7.1, 1.6 Hz, 1H), 3.13-2.99 (m, 1H), 2.74-2.55 (m, 2H), 1.79-1.61 (m, 2H), 1.38-1.24 (m, 3H), 1.06 (dt, J=72.0, 7.2 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 434 ([M+H]+).

Workup

  1. customan oven-dried three neck round bottomed flask
  2. additiontetrahydrofuran (44 mL) was added
  3. customThe stirring mixture was placed in an ice bath
  4. extractionextracted with ethyl acetate/hexanes (1:1, 2×)
  5. dry with materialThe organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. stirringThe reaction was stirred under hydrogen by balloon overnight
  9. filtrationThe reaction mixture was filtered through Celite®
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-3d833ccb5feb48418d1a2ae7675c32b9
Source dataset
uspto-grants-2016_02
Patent number
US09249133B2

Reaction notes

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