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

HRID 641105Notes

Reaction equation

HRID 641105 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].[CH:14]([CH:16]1[CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]1)=[CH2:15].Cl>C1COCC1.C1(C)C=CC=CC=1>[Cl:12][C:5]1[C:4]([F:13])=[C:3]([C:19]2([OH:22])[CH2:20][CH2:21][CH:16]([CH:14]=[CH2:15])[CH2:17][CH2:18]2)[CH:8]=[CH:7][C:6]=1[O:9][CH2:10][CH3:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5439534-EthenylcyclohexanoneHCID 5462224MagnesiumHCID 534149841-Bromo-3-chloro-4-ethoxy-2-fluorobenzene

Product 1

HCID 592569731-(3-Chloro-4-ethoxy-2-fluorophenyl)-4-vinylcyclohexanolYield 133%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
40 °C

Procedure

1.5 g of well dried magnesium and 30 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 40° C. 15.3 g of the compound (1) dissolved in 30 mL of THF was slowly added dropwise thereto at a temperature range of from 35 to 49° C., followed by stirring for 30 minutes. Thereafter, 5.0 g of the compound (23) dissolved in 5 mL of THF was slowly added dropwise thereto at a temperature range of from 30 to 40° C., followed by stirring for 30 minutes. After cooling the resulting reaction mixture to 25° C., the reaction mixture was poured into and mixed with a mixture of 100 mL of 1N hydrochloric acid and 100 mL of toluene. The mixture was separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. 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 16.0 g of 1-(3-chloro-4-ethoxy-2-fluorophenyl)-4-vinylcyclohexanol (24) as a yellow liquid.

Workup

  1. additionwas slowly added dropwise
  2. customof from 35 to 49° C.
  3. additionwas slowly added dropwise
  4. customof from 30 to 40° C.
  5. stirringby stirring for 30 minutes
  6. temperatureAfter cooling
  7. customthe resulting reaction mixture to 25° C.
  8. additionthe reaction mixture was poured into and
  9. customThe mixture was separated into an organic layer
  10. extractionextraction to the organic layer
  11. washwashed with water
  12. dry with materialby drying over anhydrous magnesium sulfate
  13. customThereafter, the solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-bf38e898c8134e688e842add4bf3be3d
Source dataset
uspto-grants-2010_04
Patent number
US07695777B2

Reaction notes

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