Trifluoroacetic acid methylene chloride → 1-(2,6-dimethyl-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acid TFA salt

HRID 2081009Notes

Reaction equation

HRID 2081009 reaction equation
[CH3:1][C:2]1[C:7]([N:8]2[CH2:12][CH:11]([C:13]([O:15]C(C)(C)C)=[O:14])[N:10]([CH3:20])[C:9]2=[O:21])=[CH:6][CH:5]=[C:4]([CH3:22])[N:3]=1.[C:23]([OH:29])([C:25]([F:28])([F:27])[F:26])=[O:24].C(Cl)Cl>>[OH:29][C:23]([C:25]([F:28])([F:27])[F:26])=[O:24].[CH3:1][C:2]1[C:7]([N:8]2[CH2:12][CH:11]([C:13]([OH:15])=[O:14])[N:10]([CH3:20])[C:9]2=[O:21])=[CH:6][CH:5]=[C:4]([CH3:22])[N:3]=1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 671036641,1-Dimethylethyl 1-(2,6-dimethyl-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 1317288121-(2,6-dimethyl-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acid TFA salt

Procedure

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (600 mg, 3.00 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 3-bromo-2,6-dimethylpyridine (557 mg, 3.00 mmol) in 1,4-dioxane (20 ml) was treated with cesium carbonate (1464 mg, 4.49 mmol), Xantphos™ (130 mg, 0.225 mmol) and tris(dibenzylideneacetone)dipalladium(0) (68.6 mg, 0.075 mmol) and the mixture was heated at reflux under argon for 3 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined, washed with water and brine and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 0-10% methanol in dichloromethane. The residue was dissolved in methanol and applied to a SCX ion exchange cartridge and washed with methanol and then 2M ammonia in methanol. The basic fractions were combined and evaporated to give 1,1-dimethylethyl 1-(2,6-dimethyl-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (493 mg, 54%). LC/MS [M+H]+=306. (ii) A solution of 1,1-dimethylethyl 1-(2,6-dimethyl-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (0.489 g, 1.6 mmol) in TFA/DCM (1:2, 9 ml) was stirred at room temperature for 16 hours. The solution was evaporated and the residue was co-evaporated with toluene and dried to give crude 1-(2,6-dimethyl-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acid TFA salt, (assume ˜1.6 mmol) which was used in the next step. LC/MS [M+H]+=250.

Workup

  1. customThe solution was evaporated
  2. customdried

Sources & evidence

ORD record
ord-0505706e04f04ea9b77782f6111c1edc
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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