Trifluoroacetic acid → HCID 131728815, compound

HRID 2081028Notes

Reaction equation

HRID 2081028 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[C:14]([N:15]2[CH2:19][C@@H:18]([C:20]([O:22]C(C)(C)C)=[O:21])[N:17]([CH3:27])[C:16]2=[O:28])=[CH:13][CH:12]=[CH:11][N:10]=1>ClCCl>[OH:5][C:3]([C:2]([F:7])([F:6])[F:1])=[O:4].[F:8][C:9]1[C:14]([N:15]2[CH2:19][CH:18]([C:20]([OH:22])=[O:21])[N:17]([CH3:27])[C:16]2=[O:28])=[CH:13][CH:12]=[CH:11][N:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67103413HCID 67103413, compound

Product 1

HCID 131728815HCID 131728815, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (400 mg, 1.998 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-fluoro-3-iodopyridine (352 mg, 1.998 mmol) in 1,4-dioxane (20 ml) was added trans-N,N-dimethylcyclohexane-1,2-diamine (0.062 ml, 0.400 mmol), potassium phosphate (1272 mg, 5.99 mmol) and copper(I) iodide (38.0 mg, 0.200 mmol) and the reaction mixture was heated at reflux under argon overnight. The reaction mixture was allowed to cool and the solvent was evaporated. The residue was partitioned between dichloromethane and water. The organic layer was separated and washed with water (˜50 ml) containing 0.880 ammonia solution (˜5 ml), then brine and passed through a hydrophobic frit and the organic layer was reduced under vacuum. The residue was purified by SP4 automated silica gel chromatography eluting with 10-80% ethyl acetate in isohexane to give 1,1-dimethylethyl 1-(2-fluoro-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (405 mg, 67.3% yield). LC/MS [M+H]+=296. (ii) Trifluoroacetic acid (2 ml) was added to a solution of 1,1-dimethylethyl (4S)-1-(2-fluoro-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (400 mg, 1.355 mmol) in dichloromethane (5 ml) and the solution was stirred at room temperature for 36 hours. The reaction mixture was reduced under vacuum and the residue was azeotroped with toluene and dried under heated vacuum to give 1-(2-fluoro-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜1.35 mmol) which was used in the next step. LC/MS [M+H]+=240.

Workup

  1. customthe residue was azeotroped with toluene
  2. customdried
  3. temperatureunder heated vacuum

Sources & evidence

ORD record
ord-e330bcb6647c446e9a6bc5138dde12b5
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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