m-Chloroperbenzoic acid → 3-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

HRID 1948516Notes

Reaction equation

HRID 1948516 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([CH:27]=[CH2:28])=[CH:23][CH:22]=4)[N:17]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=C(Cl)C=C(C(OO)=[O:37])C=1>C(Cl)Cl>[O:37]1[CH2:28][CH:27]1[C:24]1[CH:23]=[CH:22][C:21]([C:18]2[N:17]=[C:16]([C:10]3[O:9][N:8]=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:11]=3[C:12]([F:13])([F:14])[F:15])[O:20][N:19]=2)=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 66955433HCID 66955433, compound

Product 1

HCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazoleYield 97.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-3-(4-vinylphenyl)-1,2,4-oxadiazole (1.200 g, 3.13 mmol) in DCM (50 mL) was added m-CPBA (1.754 g, 7.83 mmol) in portions. The mixtures were allowed to stir at room temperature overnight. The reaction mixture was diluted with 100 ml DCM and washed with 1N NaOH. The organic layer was then dried and concentrated to provide 1.22 g of product as white solid. MS (m+1)=400. HPLC Peak RT=2.13 minutes. The two enantiomers were separated using the conditions below: Berger SFC MGIII instrument equipped with a Whelk-O 1 (25×3 cm, 5 μm). Wavelength 250 nm; Temp 35° C.; Flow rate: 150 mL/min; Mobile phase: CO2/(MeOH+0.1% DEA) in 4:1 ratio isocratic: RT=8.6 min for Peak 1 and 10.1 min for Peak 2. The absolution stereochemistry of the peak 1 (Isomer A) compound was unambiguously assigned as (S)-3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole by treating it with (S)-ethyl piperidine-3-carboxylate using the procedure found in Example 26 followed by deprotection of the ester using the procedure found in Example 14 to provide Example 14. This product matched Example 14 by 1H NMR and chiral HPLC.

Workup

  1. washwashed with 1N NaOH
  2. customThe organic layer was then dried
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-56abd53739b045e0ba8daec072b550ab
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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