Reaction #1447100

Reaction equation

KOtBu

ethyl (4-ethyl-phenyl)-acetate

1-bromo-4-cyano-3,5-difluoro-benzene

hydrochloric acid

sodium hydroxide

→

1-Bromo-4-cyano-3-methoxy-5-(4-ethyl-benzyl)-benzene

Solvents

NMP

NMP

methanol

Conditions

Workup

1. 1
   workup.ADDITIONcharged with a stir bar
2. 2
   Othermaintains below 10° C
3. 3
   workup.STIRRINGthe resulting mixture is stirred overnight at 100° C
4. 4
   workup.STIRRINGthe mixture is stirred for another h at 100° C
5. 5
   OtherThe methanol fraction is evaporated
6. 6
   workup.ADDITIONwater (200 mL) is added to the residue
7. 7
   Extractionthe resulting mixture is extracted with ethyl acetate
8. 8
   WashThe combined organic extracts are washed twice with water, twice with brine
9. 9
   Dryingdried (MgSO4)
10. 10
    OtherThe solvent is evaporated
11. 11
    Washthe residue is washed with methanol
12. 12
    OtherThe insoluble residue is separated by filtration
13. 13
    Otherdried
14. 14
    Otherto give the white product

Procedure

KOtBu (11.8 g) is added to a flask charged with a stir bar and dry NMP (40 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (10.1 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (11.5 g) in NMP (40 mL) is added at such a rate that the reaction temperature maintains below 10° C. After stirring for 1 hour at room temperature, methanol (50 mL) and 1 M aqueous sodium hydroxide solution (39 mL) are added and the resulting mixture is stirred overnight at 100° C. Then, 4 M aqueous hydrochloric acid (100 mL) is added and the mixture is stirred for another h at 100° C. The methanol fraction is evaporated, water (200 mL) is added to the residue and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are washed twice with water, twice with brine and dried (MgSO4). The solvent is evaporated and the residue is washed with methanol. The insoluble residue is separated by filtration and dried to give the white product.

Source