HCID 66955253, compound → 3-Hydroxy-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid

HRID 1948533Notes

Reaction equation

HRID 1948533 reaction equation
[O:1]1[CH2:3][CH:2]1[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[C:13]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:16]=3[C:26]([F:29])([F:28])[F:27])[O:12][N:11]=2)=[CH:6][CH:5]=1.C[Si](C)(C)[O:32][C:33]1([C:39]([O:41]C)=[O:40])[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]1>CO>[OH:32][C:33]1([C:39]([OH:41])=[O:40])[CH2:38][CH2:37][CH2:36][N:35]([CH2:3][CH:2]([OH:1])[C:4]2[CH:9]=[CH:8][C:7]([C:10]3[N:14]=[C:13]([C:15]4[O:19][N:18]=[C:17]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[C:16]=4[C:26]([F:27])([F:28])[F:29])[O:12][N:11]=3)=[CH:6][CH:5]=2)[CH2:34]1

Participants

4

Reactant 2

HCID 66955253HCID 66955253, compoundHCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 509238423-Hydroxy-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (30 mg, 0.075 mmol) in MeOH (3 mL) was added methyl 3-(trimethylsilyloxy)piperidine-3-carboxylate (100 mg, 0.432 mmol). The reaction mixture was heated at 80° C. for 2 days. The reaction mixture was concentrated in vacuo. The residue was treated with 6N HCl/MeCN at 50° 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. Isolated fractions with correct mass were freeze-dried overnight to yield 14 mg of 3-hydroxy-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-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, t, J=7.91 Hz), 7.54-7.65 (3H, m), 5.21-5.32 (1H, m), 3.69-4.01 (1H, m), 3.51 (2H, d, J=12.30 Hz), 3.33-3.43 (1H, m), 3.07-3.27 (2H, m), 2.32 (1H, br. s.), 1.78-2.08 (3H, m). MS (m+1)=545. HPLC Peak RT=3.24 minutes (Analytical Method A). Purity=95%.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionThe residue was treated with 6N HCl/MeCN at 50° C. overnight
  3. filtrationThe reaction mixture was filtered
  4. custompurified by HPLC
  5. custom25 minute
  6. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-5c64ad7799724eebb4190eee6b87d83a
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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