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

HRID 1739739Notes

Reaction equation

HRID 1739739 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 16.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of 60% w/w sodium hydride dispersion in oil (19.24 g, 1.05 mol. equiv.) in dry tetrahydrofuran (450 ml) at 0° C. under nitrogen was added a solution of 3,4-dichlorophenylacetonitrile (89.5 g, 1 mol. equiv.) in dry tetrahydrofuran (450 ml), dropwise over forty minutes. After a further thirty minutes, a solution of 2-bromoethoxytetrahydropyran (100 g , 1 mol. equiv.) in tetrahydrofuran (100 ml) was added and the mixture allowed to warm to room temperature and stirred for fourteen hours. 30% Aqueous ammonium chloride solution (500 ml) was added and the mixture extracted with diethyl ether (2×400 ml). The organic layers were combined and washed with water (2×400 ml), dried over magnesium sulphate, and the solvent removed under reduced pressure. The residue was then chromatographed using silica gel eluting with a solvent gradient of diethyl ether:hexane (1:9 to 1:1, by volume) to give the title compound (51 g). TLC Rf =0.55 (silica, methyl tert-butyl ether:hexane, 1:1, by volume). LRMS m/z=333 (m+NH4)+.

Workup

  1. waitdropwise over forty minutes
  2. waitAfter a further thirty minutes
  3. extractionthe mixture extracted with diethyl ether (2×400 ml)
  4. washwashed with water (2×400 ml)
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent removed under reduced pressure
  7. customThe residue was then chromatographed

Sources & evidence

ORD record
ord-868ca8df3b094b30ac2aca39390540c0
Source dataset
uspto-grants-1999_10
Patent number
US05968923

Reaction notes

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