Trifluoroacetic acid → HCID 22262242, compound

HRID 1610563Notes

Reaction equation

HRID 1610563 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([OH:39])[CH:16]([NH:31][C:32](=O)[O:33]C(C)(C)C)[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:30])([F:29])[CH:26]([F:28])[F:27])[N:19]=2)=[CH:11][CH:10]=1.C(=O)([O-])O.[Na+].[C:45]1(C(O)=O)[CH:46]=[CH:47][CH:48]=[C:49]2[CH2:55][CH2:54][CH2:53][CH:52]=[CH:51][C:50]=12.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]([OH:39])[CH:16]([NH:31][C:32]([C:48]2[CH:47]=[CH:46][CH:45]=[C:50]3[CH2:51][CH2:52][CH2:53][CH:54]=[CH:55][C:49]=23)=[O:33])[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:30])([F:29])[CH:26]([F:28])[F:27])[N:19]=2)=[CH:13][CH:14]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 222620106,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acidHCID 86593263HCID 86593263, compound

Product 1

HCID 22262242HCID 22262242, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoroacetic acid (3 ml) was added to tert-butyl (1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-{[6-(1,1,2,2-tetrafluoroethoxy)pyridin-2-yl]methyl}ethylcarbamate (300 mg, 0.65 mmol) at 0° C., and the mixture was stirred at 0° C. for 10 min. To the reaction solution was added saturated aqueous sodium hydrogen carbonate and the mixture was extracted with ethyl acetate (20 ml×2). The extract was washed with saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. To a solution of the residue in acetonitrile (25 ml) were added 6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid (122 mg, 0.65 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (187 mg, 0.97 mmol) and 1-hydroxybenzotriazole hydrate (99 mg, 0.65 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1). Recrystallization from ethyl acetate-hexane gave the objective substance (196 mg, 57%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 ml×2)
  2. washThe extract was washed with saturated brine
  3. dry with materialdried (anhydrous magnesium sulfate)
  4. customevaporated under reduced pressure
  5. stirringthe mixture was stirred overnight at room temperature
  6. extractionextracted with ethyl acetate (100 ml×2)
  7. washThe extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine
  8. dry with materialdried (anhydrous magnesium sulfate)
  9. customevaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1)
  11. customRecrystallization from ethyl acetate-hexane
  12. customgave the objective substance (196 mg, 57%)

Sources & evidence

ORD record
ord-f9f23f93a2814ba286700b7277922dff
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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