Water → HCID 22262011, compound

HRID 1610555Notes

Reaction equation

HRID 1610555 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8](O)[CH:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:15]=2)C(O)=O)[CH:5]=[CH:6][CH:7]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:35])C=CC=CC=1.C([N:47]([CH2:50]C)CC)C.[OH2:52]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[O:52][C:50](=[O:35])[NH:47][CH:9]2[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:25])([F:26])[CH:22]([F:23])[F:24])[CH:15]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 22261994(2RS,3RS)-3-(3-chlorophenyl)-3-hydroxy-2-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]propanoic acid

Product 1

HCID 22262011HCID 22262011, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2RS,3RS)-3-(3-chlorophenyl)-3-hydroxy-2-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]propanoic acid (4.50 g, 11.1 mmol) in tetrahydrofuran (90 ml) were added diphenylphosphoryl azide (2.62 ml, 12.2 mmol.) and triethylamine (2.32 ml, 16.6 mmol), and the mixture was heated under reflux for 4 hrs. The reaction solution was allowed to cool and water (200 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 (ethyl acetate) and neutral alumina column chromatography (ethyl acetate). Recrystallization from ethyl acetate-hexane gave the objective substance (4.70 g, 100%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 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 (ethyl acetate) and neutral alumina column chromatography (ethyl acetate)
  9. customRecrystallization from ethyl acetate-hexane
  10. customgave the objective substance (4.70 g, 100%)

Sources & evidence

ORD record
ord-6d4967253155418c8f33b8e89de4c12b
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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