Hexanenitrile, 5-oxo- → 5-Hydroxy-5-[3-(4-trifluoromethylphenyl)phenyl]hexanenitrile

HRID 440989Notes

Reaction equation

HRID 440989 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11](Br)[CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.C([Li])CCC.[O:23]=[C:24]([CH3:30])[CH2:25][CH2:26][CH2:27][C:28]#[N:29]>O1CCCC1.C(OCC)C>[OH:23][C:24]([C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:17])([F:16])[F:1])=[CH:4][CH:5]=2)[CH:10]=1)([CH3:30])[CH2:25][CH2:26][CH2:27][C:28]#[N:29]

Participants

6

Reactant 3

HCID 82611Hexanenitrile, 5-oxo-HCID 199554583-Bromo-4'-(trifluoromethyl)-1,1'-biphenylHCID 178418339Butyllithium

Product 1

HCID 199555125-Hydroxy-5-[3-(4-trifluoromethylphenyl)phenyl]hexanenitrileYield 36%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen atmosphere a stirred solution of 7.5 grams (0.025 mole) of 3-(4-trifluoromethylphenyl)phenyl bromide in 100 mL of tetrahydrofuran was cooled to about -78° C., and 10.0 mL (0.025 mole) of n-butyllithium (2.5 molar in hexane) was added dropwise. Upon completion of addition, the reaction mixture was stirred at -78° C. for about one hour. After this time a solution of 2.8 grams (0.025 mole) of 5-oxohexanenitrile in 10 mL of tetrahydrofuran was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature as it stirred for about 18 hours. After this time the reaction mixture was diluted with diethyl ether and partitioned between an aqueous dilute solution of hydrochloric acid and diethyl ether. The organic layer was separated and dried with sodium sulfate. The mixture was filtered and concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using 1:1 ethyl acetate and hexane as the eluant. The product-containing fractions were concentrated under reduced pressure, yielding about 3.0 grams of 5-hydroxy-5-[3-(4-trifluoromethylphenyl)phenyl]hexanenitrile. The NMR spectrum was consistent with the proposed structure. This reaction was repeated.

Workup

  1. additionUpon completion of addition
  2. additionUpon completion of addition
  3. temperatureto warm to ambient temperature as it
  4. stirringstirred for about 18 hours
  5. custompartitioned between an aqueous dilute solution of hydrochloric acid and diethyl ether
  6. customThe organic layer was separated
  7. dry with materialdried with sodium sulfate
  8. filtrationThe mixture was filtered
  9. concentrationconcentrated under reduced pressure to a residue
  10. concentrationThe product-containing fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-587124d8d9b74e1393cf38f2614bbb3a
Source dataset
uspto-grants-1996_05
Patent number
US05521192

Reaction notes

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