Tetrahydrofuran → HCID 66749521, compound

HRID 2402008Notes

Reaction equation

HRID 2402008 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:15]2[NH:19][CH:18]=[N:17][N:16]=2)=[C:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:6]=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>C([O-])(O)=O.[Na+]>[Br:1][C:2]1[S:3][C:4]([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)=[C:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:6]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178478057HCID 178478057, compound

Product 1

HCID 66749521HCID 66749521, compoundYield 88.5%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

In a 250 mL round bottomed flask were placed 3-[2-bromo-4-(4-chlorobenzyl)-1,3-thiazol-5-yl]-4H-1,2,4-triazole (0.7 g, 2 mmol) and tetrahydrofuran (50 mL, 600 mmol). To the mixture were added dihydropyran (2 mL, 20 mmol) and p-toluenesulfonic acid monohydrate (911.3 mg, 4.791 mmol). The mixture was refluxed for 2 h then was allowed to cool to rt and then a saturated aqueous solution of NaHCO3 (50 mL) was added. The resulting biphasic mixture was vigorously stirred for 30 min at rt. The aqueous phase was separated then was extracted with EtOAc (50 mL×2). The combined organic phases were dried over anhydrous MgSO4. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica, elution with a 10%-80% mixture of EtOAc in hexane (linear gradient, 30 min) to afford 3-[2-bromo-4-(4-chlorobenzyl)-1,3-thiazol-5-yl]-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazole (778 mg; 67% six steps) as a yellow syrup which spontaneously solidified on standing at rt for 2 days. LC/MS (FA) ES+ 441. 1H NMR (d6-DMSO, 400 MHz): δ: 8.89 (1H, s), 7.28-7.34 (4H, m), 5.62 (1H, dd, J=2.8 and 9.6 Hz), 4.52 (2H, s), 3.92-3.96 (1H, m), 3.63-3.70 (1H, m), 1.91-2.14 (3H, m), 1.52-1.72 (3H, m)

Workup

  1. customIn a 250 mL round bottomed flask were placed
  2. temperatureThe mixture was refluxed for 2 h
  3. customThe aqueous phase was separated
  4. extractionthen was extracted with EtOAc (50 mL×2)
  5. dry with materialThe combined organic phases were dried over anhydrous MgSO4
  6. customInsoluble materials were removed by filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica, elution with a 10%-80% mixture of EtOAc in hexane (linear gradient, 30 min)

Sources & evidence

ORD record
ord-3c4d5d296df54a6dae4d4a9609976d93
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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