Hydrochloric Acid → HCID 178458228, compound

HRID 1530759Notes

Reaction equation

HRID 1530759 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([F:21])[CH:15]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH2:12][CH3:13].[CH2:22]([C@H:25]1[CH2:30][CH2:29][C@H:28]([CH2:31]I)[CH2:27][CH2:26]1)[CH2:23][CH3:24].Cl>CN(C)C=O.CCCCCCC.C1(C)C=CC=CC=1>[F:3][C:4]1[CH:5]=[C:6]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:31][C@H:28]3[CH2:29][CH2:30][C@H:25]([CH2:22][CH2:23][CH3:24])[CH2:26][CH2:27]3)=[C:16]([F:21])[CH:15]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH2:12][CH3:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 21252402HCID 21252402, compoundHCID 178448079HCID 178448079, compound

Product 1

HCID 178458228HCID 178458228, compoundYield 37.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 22263336Toluene heptaneSolvent

Procedure

In a mixture of 0.7 g (60% oiliness, corresponding to 18.2 mmol) of sodium hydride and 5 ml of dimethyl formamide (DMF) was added by drops a solution of 4.0 g (15.1 mmol) of the 3,3′-difluoro-4′-hydroxy-4-propoxybiphenyl obtained in the previous step in 20 ml of DMF at room temperature, and then stirred at the same temperature for 1 hour. Subsequently, a solution of 6.0 g (22.7 mmol) of trans-4-propyl-l-iodomethylcyclohexane in 20 ml of DMF was added by drops to the reaction solution at room temperature, stirred at the same temperature for 1 hour, and then heated to reflux for 3 hours. After finishing of the reaction, the reaction solution was poured into 50 ml of a diluted hydrochloric acid and then extracted with 150 ml of toluene. The organic layer thus obtained was washed with a diluted aqueous sodium hydroxide solution thrice and with water thrice, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under a reduced pressure, and the residue thus obtained was subjected to silica gel column chromatography (eluent: heptane/toluene=7/3) to obtain 2.3 g of a crude 3,3′-difluoro-4′-((trans-4-propylcyclohexyl)methoxy)-4-propoxybiphenyl. This product was recrystallized from mixed solvent of ethanol/ethyl acetate (7/3) to obtain 1.8 g of the subject compound. (Yield: 48.2%)

Workup

  1. stirringstirred at the same temperature for 1 hour
  2. temperatureheated
  3. temperatureto reflux for 3 hours
  4. customAfter finishing of the reaction
  5. extractionextracted with 150 ml of toluene
  6. customThe organic layer thus obtained
  7. washwas washed with a diluted aqueous sodium hydroxide solution thrice and with water thrice
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off under a reduced pressure
  10. customthe residue thus obtained

Sources & evidence

ORD record
ord-c634b9d9d56f48ef9d021e0ef843bb98
Source dataset
uspto-grants-2001_03
Patent number
US06197217B1

Reaction notes

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