Trifluoroacetic acid → HCID 118293902, compound

HRID 2207657Notes

Reaction equation

HRID 2207657 reaction equation
[B-](F)(F)(F)F.[B-](F)(F)(F)F.[CH2:11]1[N+:16]2([CH2:19]Cl)[CH2:17][CH2:18][N+:13](F)([CH2:14][CH2:15]2)[CH2:12]1.CN1CC[C@]2(N=C(C3[CH:35]=[C:34]([C:36]4[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=4)[CH:33]=[CH:32][N:31]=3)CC2)C1=O.[F:49][C:50](F)([F:54])[C:51](O)=O.[OH-:56].[Na+]>CC#N>[F:49][C:50]1([F:54])[CH2:51][C@@:18]2([CH2:14][CH2:15][N:16]([CH3:19])[C:17]2=[O:56])[N:13]=[C:12]1[C:11]1[CH:35]=[C:34]([C:36]2[CH:37]=[CH:38][C:39]([C:42]([F:43])([F:44])[F:45])=[CH:40][CH:41]=2)[CH:33]=[CH:32][N:31]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 2724933SelectfluorHCID 89649163HCID 89649163, compound

Product 1

HCID 118293902HCID 118293902, compoundYield 10.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Selectfluor (1500.01 mg, 4.23 mmol) was added to a dry vial charged with (5S)-7-methyl-2-[4-[4-(trifluoromethyl)phenyl]-2-pyridyl]-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 118) (339.99 mg, 0.9100 mmol) in anhydrous MeCN (5 mL). trifluoroacetic acid (0.04 mL, 0.5300 mmol) was added to the solution. The vial was sealed under nitrogen and was heated to 90° C. for 20 h. The reaction mixture was allowed to cool to room temperature whence it was poured into sodium hydroxide (20 mL, 10 mmol). The mixture was left to stir for 10 min and extracted with ether. The combined organic layer was dried (sodium sulfate), filtered and the filtrate was evaporated to give crude brown oil (289 mg). The crude residue was purified by silica gel chromatography (10 g SiO2) eluting with ethyl acetate in iso-hexane (10-100%), followed by purification using a ChiralPak AD-H column eluting with ethanol/n-heptane (20%:80%) to give a colourless oil, (5R)-3,3-difluoro-7-methyl-2-[4-[4-(trifluoromethyl)phenyl]-2-pyridyl]-1,7-diazaspiro[4.4]non-1-en-6-one (D120) (22 mg, 0.0537 mmol, 5.9% yield);

Workup

  1. customThe vial was sealed under nitrogen
  2. temperatureto cool to room temperature whence it
  3. waitThe mixture was left
  4. extractionextracted with ether
  5. dry with materialThe combined organic layer was dried (sodium sulfate)
  6. filtrationfiltered
  7. customthe filtrate was evaporated
  8. customto give crude brown oil (289 mg)
  9. customThe crude residue was purified by silica gel chromatography (10 g SiO2)
  10. washeluting with ethyl acetate in iso-hexane (10-100%)
  11. customfollowed by purification
  12. washeluting with ethanol/n-heptane (20%:80%)

Sources & evidence

ORD record
ord-73408e7fb115429baebfea0b14b60f66
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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