Dimethyl Sulfoxide → 4-(4-Chlorophenyl)tetrahydro-2H-pyran-4-carbonitrile

HRID 47276

Reaction equation

HRID 47276 reaction equation
CS(C)=O.[H-].[Na+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]#[N:16])=[CH:10][CH:9]=1.Br[CH2:18][CH2:19][O:20][CH2:21][CH2:22]Br>C(OCC)C>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2([C:15]#[N:16])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21521Bis(2-bromoethyl) etherHCID 24758Sodium hydrideHCID 2415824-Chlorobenzyl cyanide

Product 1

HCID 219019604-(4-Chlorophenyl)tetrahydro-2H-pyran-4-carbonitrileYield 95.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
25 °C

Procedure

Into a round-bottom flask under argon fitted with an addition funnel and thermometer was added anhydrous dimethylsulfoxide (60 mL) and sodium hydride (1.17 g, 48.8 mmol, 95%). Then a solution of (4-chlorophenyl)acetonitrile (G) (3.37 g, 22.2 mmol) and 2-bromoethyl ether (90%, 3.41 mL, 24.4 mmol) in diethyl ether (15 mL) was added slowly, while maintaining the reaction temperature at 20-30° C. The reaction mixture was maintained at room temperature for overnight. The reaction mixture was carefully quenched with water (50 mL) and then extracted with hexane (3×100 mL). The organic extracts were combined, washed with water (3×75 mL), brine (50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to give a pale yellow oil. The oil was purified by column chromatography on silica gel using hexane/ethyl acetate (80:20) to give 4.7 g of 4-(4-chlorophenyl)tetrahydropyran-4-carbonitrile, H, as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 2.00-2.15 (m, 4H); 3.89 (dt, 2H, J1=12.6 Hz, J2=3 Hz); 4.05-4.11 (m, 2H); 7.37-7.45 (m, 4H); 13C NMR (CDCl3, 75 MHz): δ 36.66 (2C), 41.51, 64.98 (2C), 121.40,127.03, 129.37, 134.31, 138.46.

Workup

  1. customInto a round-bottom flask under argon fitted with an addition funnel
  2. temperatureThe reaction mixture was maintained at room temperature for overnight
  3. customThe reaction mixture was carefully quenched with water (50 mL)
  4. extractionextracted with hexane (3×100 mL)
  5. washwashed with water (3×75 mL), brine (50 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a pale yellow oil
  10. customThe oil was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-064e990e1398423f87e4d7af89a70f86
Source dataset
uspto-grants-2004_03
Patent number
US06699866B2

Linked notes

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