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

HRID 2110864Notes

Reaction equation

HRID 2110864 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 8028TetrahydrofuranSolvent2×

Procedure

A mixed solution 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 solution, and the mixture was extracted with ethyl acetate. The extract washed with aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To a mixture of the obtained oil, N-ethyldiisopropylamine (8.00 mL, 45.9 mmol) and tetrahydrofuran (50 mL) was added dropwise a solution of chloromethyl methyl ether (4.40 mL, 46.3 mmol) in tetrahydrofuran (10 mL) at 0° C. The reaction mixture was stirred overnight at room temperature, and concentrated, and the obtained residue was subjected to silica gel chromatography (ethyl acetate:hexane=1:3) to give the title compound (1.95 g, yield 35%) as a colorless oil. 1H NMR (CDCl3) δ: 1.31 (1H, t, J=7.1 Hz), 1.32 (9H, s), 3.39 (3H, s), 4.26 (2H, q, J=7.1 Hz), 4.54 (2H, s), 4.68 (2H, s), 5.70 (2H, s), 6.71 (1H, s), 7.15-7.33 (4H, m).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract washed with aqueous sodium chloride solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d6fc6efcfd7a4890b85ef08a5dc0001f
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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