Water → HCID 22261571, compound

HRID 1610589Notes

Reaction equation

HRID 1610589 reaction equation
[OH:1][CH:2]([C:21]1[CH:26]=[CH:25][C:24](OC2C=CC=CC=2)=[CH:23][N:22]=1)[CH:3]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]([F:20])([F:19])[CH:16]([F:18])[F:17])[CH:9]=1)C(O)=O.C1(P(N=[N+]=[N-])([C:42]2[CH:47]=CC=CC=2)=O)C=CC=CC=1.C([N:53]([CH2:56]C)CC)C.[OH2:58].[O:59]1[CH2:63][CH2:62][CH2:61][CH2:60]1>>[O:59]([C:24]1[CH:25]=[CH:26][C:21]([CH:2]2[O:1][C:56](=[O:58])[NH:53][CH:3]2[CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]([F:19])([F:20])[CH:16]([F:17])[F:18])[CH:9]=2)=[N:22][CH:23]=1)[C:63]1[CH:42]=[CH:47][CH:60]=[CH:61][CH:62]=1

Participants

6

Reactant 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 22261512HCID 22261512, compound

Product 1

HCID 22261571HCID 22261571, compound

Procedure

To a solution of 3-hydroxy-3-(5-phenoxypyridin-2-yl)-2-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]propanoic acid (4.22 g, 9.07 mmol, crude) in tetrahydrofuran (200 ml) were added diphenylphosphoryl azide (2.15 ml, 9.97 mmol) and triethylamine (1.90 mmol, 13.6 mmol), and the mixture was heated under reflux for 3 hrs. The reaction solution was allowed to cool and water (100 ml) was added. The mixture was extracted with ethyl acetate (100 ml×2). The extract was washed successively with 1N hydrochloric acid, aqueous sodium hydrogen carbonate solution 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) to give the objective substance in a (4RS,5RS) form (1.06 g, highly polar component, 25%) and a (4RS,5SR) form (1.94 g, less polar component, 46%, recrystallized from hexane-ethyl acetate). (4RS,5RS) form: 1H-NMR (CDCl3)δ: 2.04-2.22 (1H, m), 2.53 (1H, dd, J=14.0, 3.4 Hz), 4.38-4.50 (1H, m), 5.12 (1H, s), 5.87 (1H, d, J=8.4 Hz), 5.90 (1H, tt, J=53.2, 3.0 Hz), 6.90-7.48 (10H, m), 7.54 (1H, d, J=8.4 Hz), 8.39 (1H, d, J=2.6 Hz). IR ν maxKBrcm−1: 1761, 1588, 1574, 1487. (4RS,5SR) form: 1H-NMR (CDCl3)δ: 2.98 (1H, dd, J=13.6, 9.2 Hz), 3.28 (1H, dd, J=13.6, 4.4 Hz), 4.20-4.34 (1H, m), 5.12 (1H, brs), 5.32 (1H, d, J=5.4 Hz), 5.91 (1H, tt, J=53.2, 3.0 Hz), 7.00-7.48 (11H, m), 8.38 (1H, d, J=2.4 Hz). IR ν maxKBrcm−11761, 1588, 1576, 1489. mp 87-88° C. Anal. Calcd for C23H18F4N2O4: C, 59.74; H, 3.92; N, 6.06. Found: C, 59.70; H, 3.81; N, 6.03.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 hrs
  3. temperatureto cool
  4. extractionThe mixture was extracted with ethyl acetate (100 ml×2)
  5. washThe extract was washed successively with 1N hydrochloric acid, aqueous sodium hydrogen carbonate solution and saturated brine
  6. dry with materialdried (anhydrous magnesium sulfate)
  7. customevaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1)
  9. customto give the objective substance in a (4RS,5RS)
  10. customform (1.06 g, highly polar component, 25%) and
  11. customa (4RS,5SR) form (1.94 g, less polar component, 46%, recrystallized from hexane-ethyl acetate)
  12. custom(4RS,5RS) form

Sources & evidence

ORD record
ord-ff19f599e54f41f281b90214ea3046af
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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