Sodium Carbonate → ethyl 1-[({4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]-cyclobutanecarboxylate

HRID 623909Notes

Reaction equation

HRID 623909 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:12]=2)=[N:6][CH:7]=1.[CH3:25][C:26]1[C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][N:29]=[C:28]([O:41][CH2:42][C:43]2([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:46][CH2:45][CH2:44]2)[CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[CH3:25][C:26]1[CH:27]=[C:28]([O:41][CH2:42][C:43]2([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:46][CH2:45][CH2:44]2)[N:29]=[CH:30][C:31]=1[C:2]1[CH:7]=[N:6][C:5]([C:8]2[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:12]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 679731395-bromo-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridineHCID 67975298Ethyl 1-(((4-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl)oxy)methyl)cyclobutanecarboxylate

Product 1

HCID 67975466ethyl 1-[({4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]-cyclobutanecarboxylateYield 72.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

N,N-dimethylformamide (3 mL) was added to 5-bromo-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridine (338 mg), ethyl 1-({[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxy}methyl)-cyclobutanecarboxylate (300 mg) and palladium chloride (dppf) methylene chloride complex (33 mg), and after adding 2N aqueous sodium carbonate solution (1.2 mL) to the mixture, the atmosphere was replaced with nitrogen and the mixture was stirred at 65° C. for 2 hours. The reaction mixture was filtered by using Celite, and ethyl acetate and water were added to the filtrate to extract the objective compound. The organic layer was separated, washed with a saturated brine, and dried over anhydrous magnesium sulfate. After concentrating the mixture under reduced pressure, the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 90:10) to obtain ethyl 1-[({4-methyl-6′-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3′-bipyridin-6-yl}oxy)methyl]-cyclobutanecarboxylate (344 mg).

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionwere added to the filtrate
  3. extractionto extract the objective compound
  4. customThe organic layer was separated
  5. washwashed with a saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationAfter concentrating the mixture under reduced pressure
  8. customthe obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 90:10)

Sources & evidence

ORD record
ord-16a448e8842346db9f08b379a0504220
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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