Chloromethyl Methyl Ether → ethyl 3-tert-butyl-1-{4-[(methoxymethoxy)methyl]benzyl}-1H-pyrazole-5-carboxylate

HRID 507962Notes

Reaction equation

HRID 507962 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)C(C)C)C.[CH3:40][O:41][CH2:42]Cl>O1CCCC1.O.CN(C)C=O>[C:1]([C:5]1[CH:9]=[C:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[N:7]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][O:24][CH2:40][O:41][CH3:42])=[CH:19][CH:18]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 7864Chloromethyl Methyl EtherHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2743509Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylateHCID 5107660[4-(Chloromethyl)phenyl]methanol

Product 1

HCID 23157202ethyl 3-tert-butyl-1-{4-[(methoxymethoxy)methyl]benzyl}-1H-pyrazole-5-carboxylateYield 35.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of ethyl 3-tert-butyl-1H-pyrazole-5-carboxylate (3.00 g, 15.3 mmol), [4-(chloromethyl)phenyl]methanol (2.50 g, 16.0 mmol), potassium carbonate (2.11 g, 15.3 mmol) and N,N-dimethylformamide (40 mL) was stirred at 70° C. for 3 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a yellow oil. To a solution of the obtained oil and N-ethyldiisopropylamine (8.0 mL, 46 mmol) in tetrahydrofuran (50 mL) was added chloromethyl methyl ether (4.40 mL, 46.3 mmol) at 0° C., and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (30% ethyl acetate/hexane) to give the title compound (1.95 g. yield 35%) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto give a yellow oil
  6. stirringthe mixture was stirred overnight at room temperature
  7. concentrationThe reaction mixture was concentrated
  8. customthe residue was purified by silica gel column chromatography (30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8f8f354f28b94a0cbb6585050c8f34e0
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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