Hydrochloric Acid → 1-(3-Chloro-4-ethoxy-2-fluorophenyl)-4-pentylcyclohexanol

HRID 641095Notes

Reaction equation

HRID 641095 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([Cl:12])[C:4]=1[F:13].[CH2:14]([CH:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)[CH2:15][CH2:16][CH2:17][CH3:18].Cl>C1COCC1.C1(C)C=CC=CC=1>[Cl:12][C:5]1[C:4]([F:13])=[C:3]([C:22]2([OH:25])[CH2:21][CH2:20][CH:19]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:24][CH2:23]2)[CH:8]=[CH:7][C:6]=1[O:9][CH2:10][CH3:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5660974-PentylcyclohexanoneHCID 5462224MagnesiumHCID 534149841-Bromo-3-chloro-4-ethoxy-2-fluorobenzene

Product 1

HCID 592573781-(3-Chloro-4-ethoxy-2-fluorophenyl)-4-pentylcyclohexanolYield 102%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
43 °C

Procedure

2.9 g of well dried magnesium and 20 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 43° C. 30.0 g of 1-bromo-3-chloro-4-ethoxy-2-fluoro benzene (1) dissolved in 80 mL of THF was slowly added dropwise thereto at a temperature range of from 38 to 46° C., followed by stirring for 90 minutes. Thereafter, 19.0 g of 4-pentylcyclo hexanone dissolved in 20 mL of THF was slowly added dropwise thereto at a temperature range of from 38 to 44° C., followed by stirring for 60 minutes. After cooling the resulting reaction mixture to 30° C., the reaction mixture was mixed with 100 mL of 3N hydrochloric acid and 100 mL of toluene in a vessel and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction. The resulting organic layer was fractionated and washed with water, a 2N sodium hydroxide aqueous solution, a saturated sodium bicarbonate aqueous solution and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure to obtain 39.5 g of 1-(3-chloro-4-ethoxy-2-fluorophenyl)-4-pentylcyclohexanol (3). The resulting compound (3) was a yellow oily matter.

Workup

  1. additionwas slowly added dropwise
  2. customof from 38 to 46° C.
  3. additionwas slowly added dropwise
  4. customof from 38 to 44° C.
  5. stirringby stirring for 60 minutes
  6. temperatureAfter cooling
  7. customthe resulting reaction mixture to 30° C.
  8. customseparated into an organic layer
  9. extractionextraction
  10. washwashed with water
  11. dry with materialby drying over anhydrous magnesium sulfate
  12. customThereafter, the solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-fd6c320b86b14cb0beacc995496ad998
Source dataset
uspto-grants-2010_04
Patent number
US07695777B2

Reaction notes

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