Sodium hydride → 3-(4-Cyanophenyl)tetrahydrofuran-3-carbonitrile

HRID 1620977Notes

Reaction equation

HRID 1620977 reaction equation
[H-].[Na+].[C:3]([CH2:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=1)#[N:4].Cl[CH2:15][CH2:16][O:17][CH2:18]Cl>CN1CCCC1=O.C1COCC1>[C:10]([C:9]1[CH:12]=[CH:13][C:6]([C:5]2([C:3]#[N:4])[CH2:15][CH2:16][O:17][CH2:18]2)=[CH:7][CH:8]=1)#[N:11]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1366864-CyanophenylacetonitrileHCID 102908101-Chloro-2-(chloromethoxy)ethane

Product 1

HCID 866852363-(4-Cyanophenyl)tetrahydrofuran-3-carbonitrileYield 17.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a suspension of NaH (60% by weight, 1.2 g, 30 mmol) in 1-methylpyrrolidin-2-one (20 mL) was added a solution of 4-(cyanomethyl)benzonitrile (1.42 g, 10 mmol) and 1-chloro-2-(chloromethoxy)ethane (1.29 g, 10 mmol) in THF (10 mL) at −20° C. The mixture was allowed to warm to room temperature after completion of addition and stirred for 24 hours. The reaction was quenched by ice water and extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (3×50 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated to afford the crude product which was purified by Prep-TLC (EtOAc/hexane=1:5) to provide the title compound as a yellow oil (345 mg, 17.4%). LC-MS: m/z 172 (M−CN).

Workup

  1. additionafter completion of addition
  2. customThe reaction was quenched by ice water
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic layers were washed with water (3×50 mL), brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude product which
  9. customwas purified by Prep-TLC (EtOAc/hexane=1:5)

Sources & evidence

ORD record
ord-3f9f9421ae5b47ec906c7d0e6abd44ef
Source dataset
uspto-grants-2014_07
Patent number
US08772500B2

Reaction notes

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