Chloromethyl Methyl Ether → HCID 58598281, compound

HRID 546850Notes

Reaction equation

HRID 546850 reaction equation
[H-].[Na+].[CH2:3]([C:5]([C:27]1[CH:32]=[CH:31][C:30]([OH:33])=[C:29]([CH3:34])[CH:28]=1)([C:8]1[CH:13]=[CH:12][C:11](/[CH:14]=[CH:15]/[C:16]([OH:25])([C:21]([F:24])([F:23])[F:22])[C:17]([F:20])([F:19])[F:18])=[C:10]([CH3:26])[CH:9]=1)[CH2:6][CH3:7])[CH3:4].[CH3:35][O:36][CH2:37]Cl.[Cl-].[NH4+]>CN(C)C=O>[CH2:3]([C:5]([C:27]1[CH:32]=[CH:31][C:30]([OH:33])=[C:29]([CH3:34])[CH:28]=1)([C:8]1[CH:13]=[CH:12][C:11](/[CH:14]=[CH:15]/[C:16]([O:25][CH2:35][O:36][CH3:37])([C:21]([F:22])([F:23])[F:24])[C:17]([F:20])([F:19])[F:18])=[C:10]([CH3:26])[CH:9]=1)[CH2:6][CH3:7])[CH3:4]

Participants

6

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57452649HCID 57452649, compound

Product 1

HCID 58598281HCID 58598281, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%, 513 mg, 12.84 mmol) was added to a solution of 4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2-methyl-phenol (Example 26-(1); 5.91 g, 12.84 mmol) in N,N-dimethylformamide (60 mL) in a nitrogen atmosphere at room temperature, and the mixture was stirred for 30 minutes. Then, methoxymethyl chloride (1.45 mL, 19.26 mmol) was added, and the mixture was stirred at room temperature for 30 minutes and at 60° C. for 30 minutes. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1, 10:1 and 4:1) to give the target product as a colorless oil (2.14 g, 33%).

Workup

  1. stirringthe mixture was stirred at room temperature for 30 minutes and at 60° C. for 30 minutes
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1, 10:1 and 4:1)

Sources & evidence

ORD record
ord-b5edde44f1bd41ac9215a60e10b451ee
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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