Trifluoroacetic acid → HCID 67398914, compound

HRID 70675Notes

Reaction equation

HRID 70675 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([C:37]2[CH:42]=[CH:41][C:40]([C:43]3([OH:47])[CH2:46][CH2:45][CH2:44]3)=[C:39]([O:48]C)[N:38]=2)=[CH:19][CH:20]2[N:24](CC3C=CC(OC)=CC=3OC)[C:23](=[O:36])[CH2:22][CH2:21]2)=[CH:14][CH:13]=1)([CH3:11])([CH3:10])[CH3:9]>C1(OC)C=CC=CC=1>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([C:12]1[CH:13]=[CH:14][C:15]([C:18]([C:37]2[NH:38][C:39](=[O:48])[C:40]([C:43]3([OH:47])[CH2:44][CH2:45][CH2:46]3)=[CH:41][CH:42]=2)=[CH:19][C@H:20]2[CH2:21][CH2:22][C:23](=[O:36])[NH:24]2)=[CH:16][CH:17]=1)([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 674003365-{2-(4-Tert-butylphenyl)-2-[5-(1-hydroxycyclobutyl)-6-methoxypyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 67398914HCID 67398914, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Conditions

Temperature
85 °C

Procedure

Trifluoroacetic acid (1 mL) was added to a solution of 5-{2-(4-tert-butylphenyl)-2-[5-(1-hydroxycyclobutyl)-6-methoxypyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one (EZ mixture) (35 mg) in anisole (1 mL), and the mixture was stirred at 85° C. overnight. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→1:5). The resulting compound was dissolved in 1,4-dioxane (1 mL) and 48% hydrobromic acid (1 mL) was added, after which the mixture was stirred at 65° C. for one hour. Aqueous sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. The residue was purified by preparative HPLC (Waters Sunfire 19×150 mm 5 μm, rate: 20 mL/min, eluent: A=acetonitrile, B=0.1% trifluoroacetic acid solution, gradient: 10 to 90%) to give one isomer (A) of the title compound (1 mg, 8%) and the other isomer (B) of the title compound (1.0 mg, 8%) as colorless powders.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→1:5)
  3. dissolutionThe resulting compound was dissolved in 1,4-dioxane (1 mL)
  4. addition48% hydrobromic acid (1 mL) was added
  5. stirringafter which the mixture was stirred at 65° C. for one hour
  6. additionAqueous sodium bicarbonate was added to the reaction solution
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe organic layer was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customafter which the solvent was evaporated under reduced pressure
  11. customThe residue was purified by preparative HPLC (Waters Sunfire 19×150 mm 5 μm, rate

Sources & evidence

ORD record
ord-93cbcb8e94c74ad4bb45ca87ddeb1c13
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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