Cesium carbonate → HCID 50923566, compound

HRID 1948517Notes

Reaction equation

HRID 1948517 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([OH:16])=[O:15])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.[O:27]1C[CH:28]1[C:30]1[CH:35]=[CH:34][C:33]([C:36]2[N:40]=[C:39]([C:41]3[O:45][N:44]=[C:43]([C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)[C:42]=3[C:52]([F:55])([F:54])[F:53])[O:38][N:37]=2)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[OH:27][CH:28]([C:30]1[CH:35]=[CH:34][C:33]([C:36]2[N:40]=[C:39]([C:41]3[O:45][N:44]=[C:43]([C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)[C:42]=3[C:52]([F:55])([F:54])[F:53])[O:38][N:37]=2)=[CH:32][CH:31]=1)[CH2:6][N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([OH:16])=[O:15])[CH2:9]1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 27559654-((Tert-butoxy)carbonyl)morpholine-2-carboxylic 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 50923566HCID 50923566, compound

Conditions

Temperature
80 °C

Procedure

4-(tert-Butoxycarbonyl)morpholine-2-carboxylic acid (69.5 mg, 0.301 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 (2 mL) and DMSO (1 mL). 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole (30 mg, 0.075 mmol) and cesium carbonate (98 mg, 0.301 mmol) were added. The reaction mixture was heated at 80° C. overnight. LCMS indicated almost complete conversion to desired product and no starting material. 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. Isolated fractions with correct mass were freeze-dried overnight to yield 21 mg of 4-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)morpholine-2-carboxylic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.23 (2H, d, J=7.91 Hz), 7.69 (4H, dd, J=12.08, 7.69 Hz), 7.54-7.65 (3H, m), 5.29 (1H, td, J=6.81, 4.39 Hz), 4.41-4.65 (1H, m), 4.08-4.37 (1H, m), 3.92-4.05 (2H, m), 3.56-3.91 (1H, m), 3.44 (3H, t, J=6.81 Hz), 3.12-3.38 (1H, m). MS (m+1)=531. HPLC Peak RT=3.24 minutes (Analytical Method A). Purity=85%.

Workup

  1. customSolvents were removed in vacuo
  2. customthe resulting material was dried
  3. dissolutionThe solids were dissolved in 2-propanol (2 mL)

Sources & evidence

ORD record
ord-ed840fdcbac74ea3bf3cddbdefe673b5
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

Loading…