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

HRID 7814

Reaction equation

HRID 7814 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

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, J=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. temperaturewhile maintaining the reaction temperature at 20–30° C
  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-f8f6d6c43c6541ceab51d40476341898
Source dataset
uspto-grants-2006_08
Patent number
US07087623B2

Linked notes

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