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

HRID 2402071Notes

Reaction equation

HRID 2402071 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-c6353d2cd5974839a8e37d6a3008b5b4
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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