Hydrochloric Acid → 4-(4-Fluorophenyl)-4-hydroxy-1-phenylcyclohexanecarbonitrile

HRID 657491Notes

Reaction equation

HRID 657491 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.C([Li])CCC.[O:14]=[C:15]1[CH2:20][CH2:19][C:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:21]#[N:22])[CH2:17][CH2:16]1.Cl>C1COCC1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:15]2([OH:14])[CH2:20][CH2:19][C:18]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)([C:21]#[N:22])[CH2:17][CH2:16]2)=[CH:3][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 99931-Bromo-4-fluorobenzeneHCID 912824-Oxo-1-phenylcyclohexanenitrileHCID 178418339Butyllithium

Product 1

HCID 594425734-(4-Fluorophenyl)-4-hydroxy-1-phenylcyclohexanecarbonitrileYield 93.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

8.8 g of 1-bromo-4-fluorobenzene were dissolved in 50 ml of dry THF in a dried two-necked flask under an argon atmosphere, cooled to −70° C., and 32.2 ml of n-butyllithium solution (1.55 M in n-hexane) were slowly added dropwise so that the internal temperature did not exceed −65° C. The reaction mixture was stirred for 1 h at −70° C. Subsequently, 10.0 g of 4-oxo-1-phenylcyclohexanecarbonitrile in the form of a suspension in 50 ml of THF were slowly added dropwise so that the internal temperature did not exceed −65° C. The reaction solution was stirred further for 1 h at −70° C. and subsequently warmed to room temperature. It was stirred for 3 h at room temperature, the reaction mixture was added to ice water, cautiously acidified with 1 N hydrochloric acid and extracted three times with EA. The combined organic phases were dried over magnesium sulfate and the solvent was removed in vacuo. The crude product, a brown oil, was crystallized from toluene. 13.8 g of the title compound were obtained as a white solid.

Workup

  1. customdid not exceed −65° C
  2. customdid not exceed −65° C
  3. stirringThe reaction solution was stirred further for 1 h at −70° C.
  4. temperaturesubsequently warmed to room temperature
  5. stirringIt was stirred for 3 h at room temperature
  6. extractionextracted three times with EA
  7. dry with materialThe combined organic phases were dried over magnesium sulfate
  8. customthe solvent was removed in vacuo
  9. customThe crude product, a brown oil, was crystallized from toluene

Sources & evidence

ORD record
ord-a175e400d34f49a0ab5ba8d6ba053b73
Source dataset
uspto-grants-2011_12
Patent number
US08076324B2

Reaction notes

Loading…