Cesium carbonate → 2-(1-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)azetidin-3-yl)acetic acid

HRID 1948513Notes

Reaction equation

HRID 1948513 reaction equation
C(O[C:6]([N:8]1[CH2:11][CH:10]([CH2:12][C:13]([OH:15])=[O:14])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.[O:26]1C[CH:27]1[C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:39]=[C:38]([C:40]3[O:44][N:43]=[C:42]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[C:41]=3[C:51]([F:54])([F:53])[F:52])[O:37][N:36]=2)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[OH:26][CH:27]([C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:39]=[C:38]([C:40]3[O:44][N:43]=[C:42]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[C:41]=3[C:51]([F:54])([F:53])[F:52])[O:37][N:36]=2)=[CH:31][CH:30]=1)[CH2:6][N:8]1[CH2:9][CH:10]([CH2:12][C:13]([OH:15])=[O:14])[CH2:11]1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 110959892-(1-(Tert-butoxycarbonyl)azetidin-3-yl)acetic acidHCID 21863450Trifluoroacetic acid methylene chlorideHCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 509235652-(1-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)azetidin-3-yl)acetic acidYield 1.6%

Procedure

2-(1-(tert-Butoxycarbonyl)azetidin-3-yl)acetic acid (53.9 mg, 0.250 mmol) was treated with TFA/DCM for 1 hour. Solvents were removed in vacuo and the resulting material was dried. The solids were dissolved in 2-propanol (5 mL) and 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole (50 mg, 0.125 mmol) and cesium carbonate (245 mg, 0.751 mmol) were added. The reaction mixture was treated at 90° C. overnight. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. After concentration, the material was repurified by HPLC to yield 1 mg of 2-(1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)azetidin-3-yl)acetic acid as a TFA salt. MS (m+1)=515. HPLC Peak RT=3.24 minutes(Analytical Method A). Purity=95%.

Workup

  1. customSolvents were removed in vacuo
  2. customthe resulting material was dried
  3. dissolutionThe solids were dissolved in 2-propanol (5 mL)
  4. additionThe reaction mixture was treated at 90° C. overnight
  5. filtrationThe reaction mixture was filtered
  6. custompurified by HPLC
  7. custom25 minute
  8. concentrationAfter concentration
  9. customthe material was repurified by HPLC

Sources & evidence

ORD record
ord-37192c126c7f4d018fe0ff500611f046
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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