(Trifluoromethyl)trimethylsilane → HCID 74222541, compound

HRID 1624130Notes

Reaction equation

HRID 1624130 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][C@H:19]([CH2:22][CH2:23][CH2:24][CH3:25])[CH:20]=[O:21])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.C[Si]([C:35]([F:38])([F:37])[F:36])(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][C@H:19]([CH2:22][CH2:23][CH2:24][CH3:25])[CH:20]([OH:21])[C:35]([F:38])([F:37])[F:36])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 86717958HCID 86717958, compound

Product 1

HCID 74222541HCID 74222541, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

430 mg of 8-[(2,6-difluorobenzyl)oxy]-2-methyl-N-[(2R)-1-oxohexan-2-yl]imidazo[1,2-a]pyridine-3-carboxamide (1.05 mmol) were initially charged in 30 ml of dry THF, and 194 μl of trimethylsilyl trifluoromethane (1.24 mmol) and 621 μl of tetrabutylammonium fluoride solution (1.0 M in THF; 0.62 mmol) were successively added dropwise at 0° C. The reaction mixture was slowly warmed to RT, and stirring was continued overnight. The mixture was then concentrated and the residue was taken up in ethyl acetate, washed with saturated aqueous sodium bicarbonate solution, dried, filtered and concentrated. Preparative HPLC separation (Method 9) afforded 41 mg of the target compound, which was once more purified by HPLC (Method 10). This gave 28.4 mg of the target compound. The diastereomer ratio was about 3:1 (1H NMR integration).

Workup

  1. concentrationThe mixture was then concentrated
  2. washwashed with saturated aqueous sodium bicarbonate solution
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPreparative HPLC separation (Method 9)

Sources & evidence

ORD record
ord-d4dce23f4ade4df080e499c683ed2f48
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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