1-Methylimidazole → HCID 67046772, compound

HRID 1438395Notes

Reaction equation

HRID 1438395 reaction equation
[N:1]1([C:6]2[C:11]([CH:12]=[CH2:13])=[CH:10][CH:9]=[C:8]([C:14]([F:17])([F:16])[F:15])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN1C=CN=C1.[CH2:24]([O:26][C:27](=[O:31])[CH:28]=[N+]=[N-])[CH3:25]>C1(C)C=CC=CC=1>[N:1]1([C:6]2[C:11]([CH:12]3[CH2:13][CH:28]3[C:27]([O:26][CH2:24][CH3:25])=[O:31])=[CH:10][CH:9]=[C:8]([C:14]([F:17])([F:15])[F:16])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 13901-MethylimidazoleHCID 12192Ethyl diazoacetateHCID 67046962HCID 67046962, compound

Product 1

HCID 67046772HCID 67046772, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a THF (25 ml) suspension of methyltriphenylphosphonium bromide (3.8 g, 10.6 mmol) was added 1.60 M n-butyllithium in hexane solution (6.7 ml, 10.6 mmol) at 0° C. and the reaction was stirred for 30 minutes. Then the THF (5 ml) solution of the compound of Example 46C (1.3 g, 5.3 mmol) was added to at room temperature and stirred for 1 hour at room temperature. The reaction was quenched with saturated ammonium chloride aqueous solution, and the whole was extracted with EtOAc, dried over magnesium sulfate, and evaporated. The crude residue was purified by silica gel column chromatography, eluting with hexane/EtOAc (10:1), to give 2-pyrrolidin-1-yl-6-(trifluoromethyl)-3-vinylpyridine (1.03 g, 80%, trans). To a toluene (15 ml) solution of 2-pyrrolidin-1-yl-6-(trifluoromethyl)-3-vinylpyridine (1.03 g, 4.3 mmol), Co(TPP) (142 mg, 0.2 mmol) and 1-methyl-1H-imidazole (1.22 ml, 14.9 mmol), ethyldiazoacetate (1.0 ml, 8.5 mmol) was added and the mixture was stirred for 5 minutes at room temperature followed by additional stirring for 2 hour at 80° C. Then, evaporation and purification by silica gel column chromatography, eluting with hexane/EtOAc (20:1), gave ethyl 2-[2-pyrrolidin-1-yl-6-(trifluoromethyl)pyridin-3-yl]cyclopropanecarboxylate (1.3 g, 93%). To a THF (10 ml) solution of this compound (1.3 g, 4.0 mmol), 2M sodium hydroxide aqueous solution (15 ml) and MeOH (15 ml) were added and the mixture was stirred for 2 hours at room temperature. After the reaction was completed, the aqueous layer was extracted and then acidified with 2M HCl aqueous solution. The whole was extracted with EtOAc followed by evaporation to give the title compound (1.1 g, 92%).

Workup

  1. stirringby additional stirring for 2 hour at 80° C
  2. customThen, evaporation and purification by silica gel column chromatography
  3. washeluting with hexane/EtOAc (20:1)

Sources & evidence

ORD record
ord-af18e5e82d68481cb929e69664ba63aa
Source dataset
uspto-grants-2009_11
Patent number
US07622589B2

Reaction notes

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