Sodium hydride → 2-(2-Bromo-benzyloxy)-5-chloro-benzonitrile

HRID 2220228Notes

Reaction equation

HRID 2220228 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Br.[C:10]([C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[OH:19])#[N:11].[H-].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][O:19][C:13]1[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=1[C:10]#[N:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 769652-Bromobenzyl bromideHCID 27774205-Chloro-2-hydroxybenzonitrile

Product 1

HCID 597723822-(2-Bromo-benzyloxy)-5-chloro-benzonitrileYield 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 2-bromo-benzyl bromide (5.00 g, 20.0 mmol) and 2-cyano-4-chloro-phenol (13.2 g, 21.0 mmol) in anhydrous DMF under argon was added 95% NaH (0.56 g, 22.0 mmol) portionwise. This reaction mixture was stirred at room temperature for 1.5 hours and then quenched with water. The resulting mixture was diluted with ether (400 mL), and washed sequentially with water (3×100 mL), 1N NaOH solution (2×30 mL), saturated NaHCO3 solution (1×60 mL) and brine (1×60 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give 5.30 g of 2-(2-Bromo-benzyloxy)-5-chloro-benzonitrile Example 348A in 82% yield. HPLC Rt=3.89 min (YMC S5 ODS column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm) LC/MS: M+H=322

Workup

  1. customquenched with water
  2. additionThe resulting mixture was diluted with ether (400 mL)
  3. washwashed sequentially with water (3×100 mL), 1N NaOH solution (2×30 mL), saturated NaHCO3 solution (1×60 mL) and brine (1×60 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ef712a06b11f41ddb52241a4904b92c3
Source dataset
uspto-grants-2008_08
Patent number
US07417040B2

Reaction notes

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