Tetrahydrofuran → 2,4-Dibromo-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrile

HRID 2401809Notes

Reaction equation

HRID 2401809 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:10]2[NH:14][CH:13]=[N:12][N:11]=2)=[C:5]([Br:9])[C:6]=1[C:7]#[N:8].O1CCCC1.[O:20]1[CH:25]=[CH:24][CH2:23][CH2:22][CH2:21]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O>[Br:1][C:2]1[S:3][C:4]([C:10]2[N:14]=[CH:13][N:12]([CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25][O:20]3)[N:11]=2)=[C:5]([Br:9])[C:6]=1[C:7]#[N:8]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178509360HCID 178509360, compound

Product 1

HCID 667492652,4-Dibromo-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrileYield 84%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2,4-Dibromo-5-(4H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile (0.80 g, 2.4 mmol) was placed in a 500 mL round bottom flask and tetrahydrofuran (50 mL, 600 mmol) was added. To the resulting solution were added dihydropyran (1.31 mL, 14.4 mmol) and p-toluenesulfonic acid monohydrate (0.683 g, 3.59 mmol). The mixture was stirred for 3 h at rt. The solution was then poured into 20 mL water and extracted with 40 mL ethyl acetate twice. The combined organic layers were evaporated in vacuo. The residue was purified by column chromatography using 0-35% EtOAc in hexane to afford a solid product (0.842 g, yield 84%). LCMS: (AA) ES+, 417, 419, 421. 1H NMR (300 MHz, CDCl3) δ: 8.38 (s, 1H), 5.55-5.60 (m, 1H), 4.06-4.10 (m, 1H), 3.68-3.78 (m, 1H), 2.15-2.28 (m, 1H), 2.01-2.13 (m, 2H), 1.66-1.80 (m, 3H).

Workup

  1. extractionextracted with 40 mL ethyl acetate twice
  2. customThe combined organic layers were evaporated in vacuo
  3. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-23a3c57a2c7e455fadc56f50f026badf
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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