Hydrochloric Acid → HCID 19955494, compound

HRID 1081658Notes

Reaction equation

HRID 1081658 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5](Br)[CH:6]=[CH:7][CH:8]=1.[Mg].II.[O:15]=[C:16]([CH3:22])[CH2:17][CH2:18][CH2:19][C:20]#[N:21].Cl>O1CCCC1.O>[OH:15][C:16]([C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:11])([F:10])[F:1])[CH:4]=1)([CH3:22])[CH2:17][CH2:18][CH2:19][C:20]#[N:21]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 807IodineHCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 82611Hexanenitrile, 5-oxo-HCID 5462224Magnesium

Product 1

HCID 19955494HCID 19955494, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
35 °C

Procedure

A mixture of 7.0 mL (0.05 mole) of 3-trifluoromethylphenyl bromide, 1.2 grams (0.05 mole) of magnesium and a crystal of iodine in about 70 mL of tetrahydrofuran was warmed to 35° C. to initiate the formation of the Grignard reagent. Upon formation of the Grignard reagent, the reaction mixture was cooled to ambient temperature and, with stirring, a solution of 5.8 mL (0.05 mole) of 5-oxohexanenitrile in 10 mL of tetrahydrofuran was added dropwise. The reaction mixture temperature increased to about 35° C., at which time the rate of addition was slowed to keep the reaction mixture temperature at about 35°-40° C. The complete addition required about 15 minutes. Upon completion of the addition, the reaction mixture was allowed to warm to ambient temperature, where it was stirred for 2 hours. After this time, the reaction mixture was poured into 200 mL of water and was acidified with aqueous 2N hydrochloric acid. The mixture was then extracted with two 150 mL portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished using methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 6.3 grams of 5-hydroxy-5-(3-trifluoromethylphenyl)hexanenitrile. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionthe rate of addition
  2. customat about 35°-40° C
  3. additionThe complete addition required about 15 minutes
  4. additionUpon completion of the addition
  5. temperatureto warm to ambient temperature
  6. stirringwhere it was stirred for 2 hours
  7. extractionThe mixture was then extracted with two 150 mL portions of diethyl ether
  8. dry with materialThe combined extracts were dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure to a residual oil
  11. washElution
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0f5f0b55ec4a4a8e999a0acaeb60203e
Source dataset
uspto-grants-1996_12
Patent number
US05587379

Reaction notes

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