Dimethylformamide → methyl 3-[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]-2,2-dimethylpropanoate

HRID 623893Notes

Reaction equation

HRID 623893 reaction equation
CN(C)C=O.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=2)=[C:9]([Cl:30])[CH:8]=1.[CH3:31][C:32]([CH3:55])([CH2:37][O:38][C:39]1[CH:44]=[C:43]([CH3:45])[C:42](B2OC(C)(C)C(C)(C)O2)=[CH:41][N:40]=1)[C:33]([O:35][CH3:36])=[O:34].C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C>[Cl:30][C:9]1[CH:8]=[C:7]([C:42]2[C:43]([CH3:45])=[CH:44][C:39]([O:38][CH2:37][C:32]([CH3:31])([CH3:55])[C:33]([O:35][CH3:36])=[O:34])=[N:40][CH:41]=2)[CH:12]=[CH:11][C:10]=1[C:13]1[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 67975267Methyl 2,2-dimethyl-3-((4-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl)oxy)propanoateHCID 679753072-(4-bromo-2-chlorophenyl)-4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole

Product 1

HCID 67973607methyl 3-[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]-2,2-dimethylpropanoateYield 71.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

N,N-dimethylformamide (2 mL) was added to 2-(4-bromo-2-chlorophenyl)-4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole (297 mg), methyl 2,2-dimethyl-3-{[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxy}propanoate (228 mg) and palladium chloride (dppf) methylene chloride complex (27 mg), and after adding 2N aqueous sodium carbonate solution (0.98 mL) to the mixture, the atmosphere was replaced with nitrogen and the resulting mixture was stirred at 60° C. for 5 hours. To the reaction mixture were added ethyl acetate and water, and the liquids were separated. The organic layer was separated, washed with a saturated brine, and the residue obtained by concentrating the mixture under reduced pressure was purified by silica gel column chromatography (n-hexane:ethyl acetate=94:6 to 82:18) to obtain methyl 3-[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]-2,2-dimethylpropanoate (278 mg).

Workup

  1. customthe liquids were separated
  2. customThe organic layer was separated
  3. washwashed with a saturated brine
  4. customthe residue obtained
  5. concentrationby concentrating the mixture under reduced pressure
  6. customwas purified by silica gel column chromatography (n-hexane:ethyl acetate=94:6 to 82:18)

Sources & evidence

ORD record
ord-f45977cebd1a43c8b8e6b33a49a00f71
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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