Formic Acid → HCID 10321174, compound

HRID 2214026Notes

Reaction equation

HRID 2214026 reaction equation
[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([CH2:19][C@H:20]2[CH2:24][CH2:23][CH2:22][O:21]2)[C:10]([NH:12][C:13]2[CH:18]=[N:17][CH:16]=[CH:15][N:14]=2)=[O:11])=[CH:5][C:4]=1[C:25]([F:28])([F:27])[F:26].C(O)=[O:30].OO.[Mn]([O-])(=O)(=O)=O.[K+].[OH2:40]>CO>[CH3:1][S:2]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([CH2:19][C@H:20]2[CH2:24][CH2:23][CH2:22][O:21]2)[C:10]([NH:12][C:13]2[CH:18]=[N:17][CH:16]=[CH:15][N:14]=2)=[O:11])=[CH:5][C:4]=1[C:25]([F:28])([F:26])[F:27])(=[O:30])=[O:40]

Participants

7

Reactant 5

HCID 284Formic AcidHCID 784Hydrogen PeroxideHCID 962WaterHCID 516875Potassium PermanganateHCID 21051841HCID 21051841, compound

Product 1

HCID 10321174HCID 10321174, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-furan-2(R)-yl)-propionamide (0.054 g, 0.13 mmol) in formic acid (0.16 mL, 3.0 mmol) cooled to 0° C. was treated with a 30% aqueous hydrogen peroxide solution (0.08 mL, 0.65 mmol). The resulting solution was stirred at 0° C. for 30 min and was then quenched with a 10% aqueous sodium bisulfite solution. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (2×5 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was dissolved in methanol (1 mL) and was treated dropwise with a solution of potassium permanganate (0.023 g, 0.143 mmol) in water (0.5 mL). The dark brown solution was stirred at 25° C. for 30 min and then was diluted with methanol (10 mL). The reaction mixture was filtered to remove solids, and the filtrate was concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 7/3 hexanes/ethyl acetate to 1/1 hexanes/ethyl acetate) afforded 2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-furan-2(R)-yl)-propionamide (33 mg, 57.3%) as a colorless gum: EI-HRMS m/e calcd for C19H20F3N3O4S (M)+ 443.1127 found 443.1137.

Workup

  1. customwas then quenched with a 10% aqueous sodium bisulfite solution
  2. additionThe reaction mixture was diluted with water (5 mL)
  3. extractionextracted with ethyl acetate (2×5 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting residue was dissolved in methanol (1 mL)
  8. stirringThe dark brown solution was stirred at 25° C. for 30 min
  9. filtrationThe reaction mixture was filtered
  10. customto remove solids
  11. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-b53154696fd14c7692a1d7f4131083bb
Source dataset
uspto-grants-2006_09
Patent number
US07105671B2

Reaction notes

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