Sodium hydride → 2-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyran

HRID 844564Notes

Reaction equation

HRID 844564 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]#[N:13])[CH:7]=[CH:8][C:9]=1[Cl:10].Br[CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1.[Cl-].[NH4+]>O1CCCC1>[Cl:3][C:4]1[CH:5]=[C:6]([CH:11]([CH2:15][CH2:16][O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[C:12]#[N:13])[CH:7]=[CH:8][C:9]=1[Cl:10]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 76690(3,4-Dichlorophenyl)acetonitrileHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyran

Product 1

HCID 156708072-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyranYield 33.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of sodium hydride (60% w/w dispersion in mineral oil) (19.24 g) and anhydrous tetrahydrofuran (450 ml) at 0° C. under a nitrogen atmosphere was added a solution of 3,4-dichlorophenylacetonitrile (89.5 g) in anhydrous tetrahydrofuran (450 ml), dropwise over 40 minutes. After a further 30 minutes, a solution of 2-(2-bromoethoxy)tetrahydropyran (100 g) in anhydrous tetrahydrofuran (100 ml) was added. The mixture was allowed to warm to room temperature and then stirred for 14 hours. 30% w/w Aqueous ammonium chloride solution (500 ml) was added and the mixture extracted with diethyl ether (2×400 ml). The organic extracts were combined, washed with water (2×400 ml), dried over anhydrous magnesium sulphate and the solvent removed under reduced pressure. The residue was chromatographed on silica gel eluting with a solvent gradient of 1:9 changing to 1:1, by volume, diethyl ether:hexane to give 2-(3,4-dichlorophenyl)-4-(tetrahydropyran-2-yloxy)-butanenitrile (51 g) as an oil and as a mixture of diastereomers.

Workup

  1. waitAfter a further 30 minutes
  2. extractionthe mixture extracted with diethyl ether (2×400 ml)
  3. washwashed with water (2×400 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customthe solvent removed under reduced pressure
  6. customThe residue was chromatographed on silica gel eluting with a solvent gradient of 1:9 changing to 1:1, by volume, diethyl ether

Sources & evidence

ORD record
ord-c5c1a26f4a3048fca095ebf724926329
Source dataset
uspto-grants-2002_04
Patent number
US06380396B1

Reaction notes

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