Hydrochloric Acid → HCID 86751781, compound

HRID 1941044Notes

Reaction equation

HRID 1941044 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].[O:14]1[CH2:19][CH2:18][CH2:17][O:16][CH:15]1[CH2:20][CH2:21][CH:22]1[CH2:27][CH2:26][CH:25]([CH2:28][CH2:29]O)[CH2:24][CH2:23]1.Cl.C(O)CCO>CCOCC>[O:14]1[CH2:19][CH2:18][CH2:17][O:16][CH:15]1[CH2:20][CH2:21][CH:22]1[CH2:23][CH2:24][CH:25]([CH:28]=[CH:29][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]([F:12])([F:11])[F:10])=[C:2]([F:1])[CH:3]=2)[CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 104421,3-PropanediolHCID 27822174-Bromo-2-fluoro-1-(trifluoromethoxy)benzeneHCID 53700305HCID 53700305, compound

Product 1

HCID 86751781HCID 86751781, compoundYield 52.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

A Grignard reagent prepared from 3-fluoro-4-trifluoromethoxybromobenzene (9.3 g, 38.7 mmol) and dried Mg (0.97 g 39.9 mmol) in a 50 ml ether solvent, was cooled down 0° C., followed by dropwise adding thereto, a 40 ml ether solution of the above 2-(4-(1,3-dioxan-2-ylethyl)cyclohexyl)ethanol (6.3 g, 26.2 mmol), heating the mixture up to room temperature, stirring it for 3 hours, adding this reaction solution to 6N HCl (100 ml), extracting the resulting product with ethyl acetate, washing the extraction solution successively with a saturated aqueous solution of sodium bicarbonate and water, drying over MgSO4, distilling off the solvent, adding toluene (150 ml) and Amberlist (3.0 g) to the residue, refluxing for 5 hours, while removing water formed by the reaction by means of Dean-Stark, adding trimethylene glycol (1.0 g, 13.1 mmol), further refluxing for one hour, filtering off Amberlist, distilling off the solvent, purifying the residue according to column chromatography treatment using ethyl acetate/toluene (1/2) as a developing solvent, on silica gel, and distilling off the solvent, to isolate 1-(2-(4-(1,3-dioxan-2-ylethyl)cyclohexyl)vinyl-3-fluoro-4-trifluoromethoxybenzene (5.5 g, 13.7 mmol). The yield of this product from 2-(4-(1,3-dioxan-2-ylethyl)cyclohexyl)ethanol was 52.3%.

Workup

  1. additionby dropwise adding
  2. extractionextracting the resulting product with ethyl acetate
  3. washwashing the extraction solution successively with a saturated aqueous solution of sodium bicarbonate and water
  4. dry with materialdrying over MgSO4
  5. distillationdistilling off the solvent
  6. additionadding toluene (150 ml) and Amberlist (3.0 g) to the residue
  7. temperaturerefluxing for 5 hours
  8. customwhile removing water
  9. customformed by the reaction by means of Dean-Stark
  10. temperaturefurther refluxing for one hour
  11. filtrationfiltering off Amberlist
  12. distillationdistilling off the solvent
  13. custompurifying the residue
  14. distillationon silica gel, and distilling off the solvent

Sources & evidence

ORD record
ord-800668de0e38448aabb3a9506b1a7fbd
Source dataset
uspto-grants-1997_12
Patent number
US05702641

Reaction notes

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