Ammonia → HCID 22709034, compound

HRID 352276Notes

Reaction equation

HRID 352276 reaction equation
[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][C:14]([F:21])=[CH:15][C:16]=3[F:20])[CH2:11]2)=[CH:6][CH:5]=1)[CH2:2][CH3:3].[CH2:22]([Li])CCC.C(O)(=O)C1C=CC=CC=1.C(=O)=O.S(Cl)(Cl)=O.[NH3:43].P(Cl)(Cl)(Cl)=O.Cl>CN(C=O)C.O>[CH2:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][C:14]([F:21])=[C:15]([C:22]#[N:43])[C:16]=3[F:20])[CH2:11]2)=[CH:8][CH:9]=1)[CH2:2][CH3:3]

Participants

11

Reactant 8

HCID 222AmmoniaHCID 243Benzoic AcidHCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 24813Phosphorus oxychlorideHCID 22709044HCID 22709044, compoundHCID 178418339Butyllithium

Product 1

HCID 22709034HCID 22709034, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under the same conditions as those described for the example 1, using 3,5-difluorophenylacetic acid instead of 4-fluorophenylacetic acid yielded 2-(4-propylphenyl)-5,7-difluoro-1,2,3,4-tetrahydronaphthalene. 10 g of this 2-(4-propylphenyl)-5,7-difluoro-1,2,3,4-tetrahydronaphthalene was lithiated using butyllithium, converted to a benzoic acid by blowing carbon dioxide into the reaction vessel, subsequently converted to an acid chloride with thionyl chloride, and an amide then synthesized by blowing ammonia gas into the reaction mixture was dissolved in 40 ml of DMF, 2.5 ml of phosphorus oxychloride was added, and the reaction was allowed to proceed for 2 hours at 25° C. The reaction liquid was poured into water with ice, dilute hydrochloric acid was added, and the water layer was extracted with toluene. The toluene extract was combined with the organic layer, and following washing with water, a saturated aqueous solution of sodium bicarbonate, water and a saturated aqueous solution of sodium chloride, was dried over anhydrous sodium sulfate. The crude product was purified using silica gel column chromatography (hexane/dichloromethane=6/4), and then recrystallized from ethanol to yield 6.3 g of 2-(4-propylphenyl)-5,7-difluoro-6-cyano-1,2,3,4-tetrahydronaphthalene.

Workup

  1. customThe reaction liquid
  2. additionwas added
  3. extractionthe water layer was extracted with toluene
  4. extractionThe toluene extract
  5. washfollowing washing with water
  6. dry with materiala saturated aqueous solution of sodium bicarbonate, water and a saturated aqueous solution of sodium chloride, was dried over anhydrous sodium sulfate
  7. customThe crude product was purified
  8. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-2bcd9f5ec3d64a8489b222e985f32df6
Source dataset
uspto-grants-2004_06
Patent number
US06746728B1

Reaction notes

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