Propargyl alcohol → N-[3-(3-hydroxyprop-1-yn-1-yl)pyrazin-2-yl]-2-(trifluoromethyl)benzenesulfonamide

HRID 2401031Notes

Reaction equation

HRID 2401031 reaction equation
Cl[C:2]1[C:3]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:20])[F:19])(=[O:11])=[O:10])=[N:4][CH:5]=[CH:6][N:7]=1.[CH2:22]([OH:25])[C:23]#[CH:24].CC(O[K])=O>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:25][CH2:22][C:23]#[C:24][C:2]1[C:3]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:20])[F:19])(=[O:11])=[O:10])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

7

Reactant 3

HCID 7859Propargyl alcoholHCID 57586069N-(3-chloropyrazin-2-yl)-2-(trifluoromethyl)benzenesulfonamideHCID 178476685HCID 178476685, compound

Product 1

HCID 57444251N-[3-(3-hydroxyprop-1-yn-1-yl)pyrazin-2-yl]-2-(trifluoromethyl)benzenesulfonamideYield 50%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

N-(3-chloropyrazin-2-yl)-2-(trifluoromethyl)benzenesulfonamide (1.35 g; 4.0 mmol; 1.00 eq.) and 2-propyn-1-ol (336 mg 6.0 mmol; 1.5 eq.) were dissolved in 10 mL of DMF under nitrogen atmosphere. To the reaction mixture was added CH3COOK (588 mg; 6.0 mmol; 1.5 eq.) CuI (40 mg; 0.2 mmol; 0.05 eq.) and Pd(PPh3)2Cl2 (28 mg; 0.04 mmol) under nitrogen. The reaction mixture was then heated at 100° C. under nitrogen for 2 hours. After removal of the solvent by distillation in vacuo, the residue was triturated with water (40 mL) and extracted with diethyl ether (3×30 mL). The organic layer was dried over MgSO4 and evaporated down. The crude product was purified by silica gel column chromatography using a mixture of hexane and AcOEt to give pure N-[3-(3-hydroxyprop-1-yn-1-yl)pyrazin-2-yl]-2-(trifluoromethyl)benzenesulfonamide as a yellowish solid (702 mg, 50% yield, 98% HPLC purity).

Workup

  1. customAfter removal of the solvent
  2. distillationby distillation in vacuo
  3. customthe residue was triturated with water (40 mL)
  4. extractionextracted with diethyl ether (3×30 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. customevaporated down
  7. customThe crude product was purified by silica gel column chromatography
  8. additiona mixture of hexane and AcOEt

Sources & evidence

ORD record
ord-375084f141a54e6a90c69d261898da8e
Source dataset
uspto-grants-2014_08
Patent number
US08796280B2

Reaction notes

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