Trifluoroacetic acid → HCID 22261416, compound

HRID 1610606Notes

Reaction equation

HRID 1610606 reaction equation
[OH:1][CH:2]([C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)=[CH:28][CH:27]=1)[CH:3]([NH:18][C:19](=O)[O:20]C(C)(C)C)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:17])([F:16])[CH:13]([F:15])[F:14])[CH:6]=1.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+].[F:51][C:52]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[C:55](C(O)=O)=[CH:54][CH:53]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:51][C:52]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[C:55]([C:19]([NH:18][CH:3]([CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:17])([F:16])[CH:13]([F:14])[F:15])[CH:6]=2)[CH:2]([OH:1])[C:26]2[CH:27]=[CH:28][C:29]([O:32][C:33]3[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=3)=[CH:30][CH:31]=2)=[O:20])=[CH:54][CH:53]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 684484-Fluoro-1-naphthoic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86593279HCID 86593279, compound

Product 1

HCID 22261416HCID 22261416, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To tert-butyl (1RS,2SR)-2-hydroxy-2-[4-(pyridin-3-yloxy)phenyl]-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethylcarbamate (500 mg, 0.93 mmol) was added trifluoroacetic acid (10 ml), and the mixture was stirred at 0° C. for 10 min. The reaction solution was neutralized with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate (30 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 (20 ml) were added 4-fluoronaphthalenecarboxylic acid (177 mg, 0.93 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (268 mg, 1.40 mmol) and 1-hydroxybenzotriazole hydrate (143 mg, 0.93 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (150 ml), and the mixture was extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-1:1). Recrystallization from ethyl acetate-hexane gave the objective substance (347 mg, 61%).

Workup

  1. extractionextracted with ethyl acetate (30 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. extractionthe mixture was extracted with ethyl acetate (100 ml×2)
  7. washThe extract was washed successively with water 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=4:1-1:1)
  11. customRecrystallization from ethyl acetate-hexane
  12. customgave the objective substance (347 mg, 61%)

Sources & evidence

ORD record
ord-a592c2e148f74399a346aeb93929a189
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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