Sodium Iodide → 4-[5-(4-cyano-3-fluoro-phenoxy)pentyloxy]-N,N-bis(1-methylethyl)benzamide

HRID 2209742Notes

Reaction equation

HRID 2209742 reaction equation
[OH:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.Br[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]Cl.C(=O)([O-])[O-].[Cs+].[Cs+].[F:30][C:31]1[CH:38]=[C:37]([OH:39])[CH:36]=[CH:35][C:32]=1[C:33]#[N:34].[H-].[Na+].[I-].[Na+]>CN(C)C=O>[C:33]([C:32]1[CH:35]=[CH:36][C:37]([O:39][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:1][C:2]2[CH:16]=[CH:15][C:5]([C:6]([N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]([CH3:10])[CH3:11])=[O:7])=[CH:4][CH:3]=2)=[CH:38][C:31]=1[F:30])#[N:34]

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 960701-Bromo-5-chloropentaneHCID 27346752-Fluoro-4-hydroxybenzonitrileHCID 218414724-hydroxy-N,N-bis(propan-2-yl)benzamide

Product 1

HCID 193814994-[5-(4-cyano-3-fluoro-phenoxy)pentyloxy]-N,N-bis(1-methylethyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A stirred solution of 4-hydroxy-N,N-bis(1-methylethyl)benzamide (500 mg, 2.3 mmol) in 5 mL of N,N-dimethylformamide is treated with 1-bromo-5-chloropentane (300 μL, 2.3 mmol) and cesium carbonate (750 mg, 2.3 mmol) and heated for 2 hours. This is treated with a mixture of 2-fluoro-4-hydroxy-benzonitrile, and 60% sodium hydride (92 mg, 2.3 mmol) in 2 mL of N,N-dimethylformaide followed by sodium iodide (1.04 g, 6.9 mmol). The reaction is heated to 70° C. for 6 hours and partitioned between ethyl acetate and water. The organic phase is washed with brine, dried over sodium sulfate, and concentrated in vacuo. The resulting material is purified by chromatography on silica gel (20 g) with 70% ethyl acetate/hexane as the eluent to afford 4-[5-(4-cyano-3-fluoro-phenoxy)pentyloxy]-N,N -bis(1-methylethyl)benzamide.

Workup

  1. temperatureheated for 2 hours
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase is washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting material is purified by chromatography on silica gel (20 g) with 70% ethyl acetate/hexane as the eluent

Sources & evidence

ORD record
ord-8966da142b98419c8f0b4b9ef2ab6e85
Source dataset
uspto-grants-1995_10
Patent number
US05455274

Reaction notes

Loading…