Tetrahydrofuran → (4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)methanone

HRID 2401721Notes

Reaction equation

HRID 2401721 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:14]=[CH:13][S:12][C:11]=2[C:15]2[NH:19][CH:18]=[N:17][N:16]=2)=[O:9])=[CH:4][CH:3]=1.O1CCCC1.[O:25]1[CH:30]=[CH:29][CH2:28][CH2:27][CH2:26]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:14]=[CH:13][S:12][C:11]=2[C:15]2[N:19]=[CH:18][N:17]([CH:26]3[CH2:27][CH2:28][CH2:29][CH2:30][O:25]3)[N:16]=2)=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178519587(4-chlorophenyl)[2-(4H-1,2,4-triazol-3-yl)-3-thienyl]methanone

Product 1

HCID 66749278(4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)methanone

Procedure

In a 500 mL, round bottomed flask, (4-chlorophenyl)[2-(4H-1,2,4-triazol-3-yl)-3-thienyl]methanone (16.89 g, 58.29 mmol) was dissolved in tetrahydrofuran (500.0 mL, 6164 mmol). To the solution were added dihydropyran (31.9 mL, 3.50E2 mmol) and p-toluenesulfonic acid monohydrate (16.6 g, 87.4 mmol). The mixture was stirred for 3 h at rt. The reaction was quenched by the addition of saturated aqueous solution of sodium bicarbonate (200 mL). The aqueous phase was separated and then extracted with EtOAc (300 mL). The combined organic phases were dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to afford (4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)methanone as an oil which was dried under high vacuum overnight (19.4, 89.1%). LCMS: (FA) ES+ 374.2, 376.1.

Workup

  1. customThe reaction was quenched by the addition of saturated aqueous solution of sodium bicarbonate (200 mL)
  2. customThe aqueous phase was separated
  3. extractionextracted with EtOAc (300 mL)
  4. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
  5. customThe drying agent was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-ba4b106a62a14a6fa8115a21fdb41196
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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