Chloromethyl Methyl Ether → 2-Fluoro-3-((4-propylcyclohexyl)phenyl)-1-methoxymethoxybenzene

HRID 17752Notes

Reaction equation

HRID 17752 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16]2[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH3:24])[CH2:18][CH2:17]2)=[CH:8][CH:7]=[CH:6][C:5]=1[OH:25].[CH3:26][O:27][CH2:28]Cl>C1COCC1.O>[F:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16]2[CH2:17][CH2:18][CH:19]([CH2:22][CH2:23][CH3:24])[CH2:20][CH2:21]2)=[CH:8][CH:7]=[CH:6][C:5]=1[O:25][CH2:26][O:27][CH3:28]

Participants

6

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 684292922-Fluoro-3-((4-propylcyclohexyl)phenyl)phenol

Product 1

HCID 684269072-Fluoro-3-((4-propylcyclohexyl)phenyl)-1-methoxymethoxybenzeneYield 107.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, 1.52 g of sodium hydride was added to 9.45 g of 2-fluoro-3-((4-propylcyclohexyl)phenyl)phenol (5) dissolved in 60 mL of THF cooling with iced water, and the mixture was stirred at ambient temperature for 30 minutes. 3.07 g of chloromethyl methyl ether was added to the solution under cooling with iced water, followed by stirring at ambient temperature for 4 hours. After terminating the reaction by pouring water into the reaction solution, the aqueous layer was extracted with toluene, which was added to the organic layer, and the organic layer was washed with a saturated salt solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain 11.6 g of 2-fluoro-3-((4-propylcyclohexyl)phenyl)-1-methoxymethoxybenzene (6).

Workup

  1. stirringby stirring at ambient temperature for 4 hours
  2. customAfter terminating
  3. customthe reaction
  4. extractionthe aqueous layer was extracted with toluene, which
  5. additionwas added to the organic layer
  6. washthe organic layer was washed with a saturated salt solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled off

Sources & evidence

ORD record
ord-b88aec028ab3465a9637eaaccef53927
Source dataset
uspto-grants-2010_06
Patent number
US07740769B2

Reaction notes

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