7-Methoxy-1,2,3,4-tetrahydronaphthalen-1-one → 7-Methoxynaphthalene-1-carbonitrile

HRID 226269Notes

Reaction equation

HRID 226269 reaction equation
FC1C=C([C:9]2[CH:10]=[C:11]([C:20]#[N:21])[C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[C:14]([OH:19])[CH:13]=3)C=CC=1O.[CH3:22]OC1C=C2C(CCCC2=O)=CC=1>C1(C)C=CC=CC=1>[CH3:22][O:19][C:14]1[CH:13]=[C:12]2[C:17]([CH:18]=[CH:9][CH:10]=[C:11]2[C:20]#[N:21])=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 812767-Methoxy-1,2,3,4-tetrahydronaphthalen-1-oneHCID 61026913-(3-Fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile

Product 1

HCID 113443927-Methoxynaphthalene-1-carbonitrile

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

In a highly preferred aspect of this invention illustrated in Scheme 1, there is provided a new and improved process for the large-scale production of 3-(3-fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile (1). Commercial material 3,4-dihydro-7-methoxy-1(2H)-naphthalenone (7-methoxy-1-tetralone) may be transformed into an unsaturated nitrile (3) as shown on Scheme 1. The reaction is performed in toluene solution. Upon the completion of the reaction, it is quenched by caustic solution. The reaction mixture is extracted with toluene. After washing the toluene solution, the crude unsaturated nitrile (3) is aromatized directly in this toluene solution by stirring with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) at 60° C. for 2 h. The solid is removed by filtration and the filtrate is washed with sodium hydroxide solution and brine and respectively. Most of the solvent is removed by distillation and heptane is added to precipitate the product. 7-methoxy-1-naphthonitrile (4) is isolated. The expected yield over these two steps is at least 70-75%. By performing two reactions in the same solvent, isolation of the low melting point intermediate (3) can be avoided, improving efficiency and yield.

Workup

  1. customUpon the completion of the reaction, it
  2. customis quenched by caustic solution
  3. extractionThe reaction mixture is extracted with toluene
  4. washAfter washing the toluene solution
  5. customThe solid is removed by filtration
  6. washthe filtrate is washed with sodium hydroxide solution and brine
  7. customMost of the solvent is removed by distillation and heptane
  8. additionis added
  9. customto precipitate the product

Sources & evidence

ORD record
ord-695cb9dbe6894511be953e5c9b09923a
Source dataset
uspto-grants-2009_07
Patent number
US07557237B2

Reaction notes

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