Bis(2-bromoethyl) ether → 4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-carbonitrile

HRID 1397204Notes

Reaction equation

HRID 1397204 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([CH2:12][C:13]#[N:14])[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:18][CH2:19][O:20][CH2:21][CH2:22]Br>C1COCC1>[C:1]1([C:7]2[N:8]=[C:9]([C:12]3([C:13]#[N:14])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[S:10][CH:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 21521Bis(2-bromoethyl) etherHCID 24758Sodium hydrideHCID 704539(4-Phenyl-1,3-thiazol-2-yl)acetonitrile

Product 1

HCID 673223044-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-carbonitrileYield 85.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(4-phenylthiazol-2-yl)acetonitrile (0.84 g, 4.19 mmol) in THF (25 mL) was cooled to 0° C. NaH was added (0.5 g, 60% dispersion in oil) portionwise over 10 min. The resulting mixture was allowed to warm up to room temperature and stirred for 20 min. 2-Bromoethyl ether (1.58 mL, 12.5 mmol) was added dropwise. The reaction mixture was further stirred at room temperature for 1 h and then quenched with saturated NH4Cl solution. The reaction mixture was diluted with EtOAc and the organic layer was washed with H2O and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 60-120 mesh, eluent 4-8% EtOAc in petroleum ether) to afford 4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-carbonitrile (0.97 g, yield 85%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.91-7.94 (m, 2H), 7.51 (s, 1H), 7.37-7.48 (m, 3H), 4.07-4.14 (m, 2H), 3.87-3.96 (m, 2H), 2.32-2.43 (m, 4H). MS (ESI) m/z: Calculated for C15H14N2OS: 270.08. found: 271.2 (M+H)+.

Workup

  1. stirringThe reaction mixture was further stirred at room temperature for 1 h
  2. customquenched with saturated NH4Cl solution
  3. additionThe reaction mixture was diluted with EtOAc
  4. washthe organic layer was washed with H2O and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (silica gel 60-120 mesh, eluent 4-8% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-3eecba122fd946ac9bb8d3767ee645c5
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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