1-[({4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]-cyclobutanecarboxylic acid → 1-[({4-methyl-6'-[5-(trifluoromethyl)-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylic acid

HRID 623911Notes

Reaction equation

HRID 623911 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2([C:14]([OH:16])=[O:15])[CH2:13][CH2:12][CH2:11]2)[N:5]=[CH:4][C:3]=1[C:17]1[CH:18]=[N:19][C:20]([C:23]2[N:24](COCC[Si](C)(C)C)[CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[N:27]=2)=[CH:21][CH:22]=1>FC(F)(F)C(O)=O.O>[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2([C:14]([OH:16])=[O:15])[CH2:13][CH2:12][CH2:11]2)[N:5]=[CH:4][C:3]=1[C:17]1[CH:18]=[N:19][C:20]([C:23]2[NH:27][C:26]([C:28]([F:30])([F:29])[F:31])=[CH:25][N:24]=2)=[CH:21][CH:22]=1

Participants

4

Reactant 1

HCID 679753041-[({4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]-cyclobutanecarboxylic acid

Product 1

HCID 679752891-[({4-methyl-6'-[5-(trifluoromethyl)-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylic acidYield 86.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

In trifluoroacetic acid (3.3 mL) and water (0.33 mL) was dissolved 1-[({4-methyl-6′-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3′-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylic acid (327 mg), and the solution was stirred at room temperature for 60 hours. The reaction mixture was concentrated under reduced pressure, subjected to azeotropic distillation with acetic acid, and isopropyl ether was added to the obtained residue. The precipitated solid was collected by filtration and dried under reduced pressure to obtain 1-[({4-methyl-6′-[5-(trifluoromethyl)-1H-imidazol-2-yl]-3,3′-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylic acid (217 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. distillationsubjected to azeotropic distillation with acetic acid, and isopropyl ether
  3. additionwas added to the obtained residue
  4. filtrationThe precipitated solid was collected by filtration
  5. customdried under reduced pressure

Sources & evidence

ORD record
ord-67ca18c5a63f4e539f4a8a1ed1dd94be
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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