Bis(2-chloroethyl) ether → 4-(3-(trifluoromethyl)phenyl)tetrahydro-2H-pyran-4-carbonitrile

HRID 2078143Notes

Reaction equation

HRID 2078143 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]([F:19])([F:18])[C:9]1[CH:10]=[C:11]([CH2:15][C:16]#[N:17])[CH:12]=[CH:13][CH:14]=1.Cl[CH2:21][CH2:22][O:23][CH2:24][CH2:25]Cl>CN(C=O)C>[F:7][C:8]([F:18])([F:19])[C:9]1[CH:10]=[C:11]([C:15]2([C:16]#[N:17])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 8115Bis(2-chloroethyl) etherHCID 75360m-TrifluoromethylphenylacetonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 431190344-(3-(trifluoromethyl)phenyl)tetrahydro-2H-pyran-4-carbonitrileYield 162.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium tert-butoxide (4.00 g, 35.6 mmol, 2.20 eq) was added to a stirred solution of 2-(3-(trifluoromethyl)phenyl)acetonitrile (2.53 mL, 16.2 mmol, 1.0 eq) in DMF (30 mL) at 0° C. under a nitrogen atmosphere. The mixture was stirred for 10 minutes at 0° C. before 1-chloro-2-(2-chloroethoxy)ethane (2.09 mL, 17.8 mmol, 1.1 eq) was added dropwise via syringe. The reaction mixture was allowed to warm to room temperature and stirred for 6 hours. The reaction mixture was then cooled to 0° C. and quenched with 10% HCl. The aqueous mixture was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), and concentrated in vacuo to give the product as an orange oil (6.73 g).

Workup

  1. additionwas added dropwise via syringe
  2. temperatureThe reaction mixture was then cooled to 0° C.
  3. customquenched with 10% HCl
  4. extractionThe aqueous mixture was extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5ed30b8c85f64632a39b32faf2919740
Source dataset
uspto-grants-2011_04
Patent number
US07928139B2

Reaction notes

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