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

HRID 2080985Notes

Reaction equation

HRID 2080985 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([O:9]C(C)(C)C)=[O:8])[CH2:5][N:4]([C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=2)[C:3]1=[O:21].[C:22]([OH:28])([C:24]([F:27])([F:26])[F:25])=[O:23].C(Cl)Cl>>[OH:28][C:22]([C:24]([F:27])([F:26])[F:25])=[O:23].[CH3:1][N:2]1[CH:6]([C:7]([OH:9])=[O:8])[CH2:5][N:4]([C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=2)[C:3]1=[O:21]

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 671035671,1-Dimethylethyl 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 1317288073-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylic acid TFA salt

Procedure

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (600 mg, 3 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-bromo-3-methylpyridine (515 mg, 3 mmol) in 1,4-dioxane (20 ml) was treated with cesium carbonate (1464 mg, 4.5 mmol), Xantphos™ (130 mg, 0.225 mmol) and tris(dibenzylideneacetone)dipalladium(0) (68.6 mg, 0.075 mmol) and the mixture was heated under reflux under argon for 18 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 0-100% ethyl acetate in isohexane to give 1,1-dimethylethyl 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (700 mg, 80%). LC/MS [M+H]+=292. (ii) A solution of 1,1-dimethylethyl 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (700 mg, 2.4 mmol) in TFA/DCM (1:2, 12 ml) was stirred at room temperature for 6 hours. The solution was evaporated and the residue was co-evaporated with toluene and dried to give 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜2.4 mmol) which was used in the next step. LC/MS [M+H]+=236.

Workup

  1. customThe solution was evaporated
  2. customdried

Sources & evidence

ORD record
ord-ac105275dd774e80a9c5b2c6733cea9d
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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