Water → {4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-acetonitrile

HRID 1862497Notes

Reaction equation

HRID 1862497 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]O)=[CH:4][C:3]=1[O:10][CH3:11].[C-:12]#[N:13].[Na+].Br[CH2:16][CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1.O>CN(C)C=O>[F:25][C:22]1[CH:23]=[CH:24][C:19]([O:18][CH2:17][CH2:16][O:1][C:2]2[CH:9]=[CH:8][C:5]([CH2:6][C:12]#[N:13])=[CH:4][C:3]=2[O:10][CH3:11])=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8929Sodium CyanideHCID 62348Vanillyl alcoholHCID 20641711-(2-Bromoethoxy)-4-fluorobenzene

Product 1

HCID 18619854{4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-acetonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-hydroxy-3-methoxy-benzyl alcohol (14.7 g) and sodium cyanide (5 g) in dimethylformamide (200 ml) is stirred under an atmosphere of nitrogen for 3 hours at +120° C. The mixture is then cooled to +100° C. and 1-(2-bromo-ethoxy)-4-fluoro-benzene (25 g) is added in one portion. The mixture is stirred at +100° C. for another 4 hours. Upon cooling water (800 ml) is added. The mixture is extracted with ethyl acetate (2×500 ml). The organic phases are washed with brine (2×500 ml), dried (MgSO4) and evaporated. The residue is recrystallised from ethyl acetate/hexane. {4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-acetonitrile is obtained, m.p. 126-128° C.

Workup

  1. temperatureThe mixture is then cooled to +100° C.
  2. stirringThe mixture is stirred at +100° C. for another 4 hours
  3. additionis added
  4. extractionThe mixture is extracted with ethyl acetate (2×500 ml)
  5. washThe organic phases are washed with brine (2×500 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue is recrystallised from ethyl acetate/hexane

Sources & evidence

ORD record
ord-3647f740f1d54730b58192054d832424
Source dataset
uspto-grants-2003_03
Patent number
US06538016B2

Reaction notes

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