Tetrahydrofuran → (S)-ethyl 1-((S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate

HRID 1948527Notes

Reaction equation

HRID 1948527 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12](F)=[O:13])[C:8]=2[C:15]([F:18])([F:17])[F:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1.[OH:42][C@@H:43]([C:56]1[CH:61]=[CH:60][C:59](/[C:62](=[N:64]/O)/[NH2:63])=[CH:58][CH:57]=1)[CH2:44][N:45]1[CH2:50][CH2:49][CH2:48][C@H:47]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:46]1>C(#N)C.C(OCC)(=O)C>[OH:42][C@@H:43]([C:56]1[CH:61]=[CH:60][C:59]([C:62]2[N:64]=[C:12]([C:9]3[C:8]([C:15]([F:18])([F:17])[F:16])=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[O:11][N:10]=3)[O:13][N:63]=2)=[CH:58][CH:57]=1)[CH2:44][N:45]1[CH2:50][CH2:49][CH2:48][C@H:47]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:46]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 58374105HCID 58374105, compoundHCID 58374160HCID 58374160, compound

Product 1

HCID 86656399(S)-ethyl 1-((S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride, Int-II-D (78 mg, 0.3 mmol) was dissolved in acetonitrile (5 mL) and (S)-ethyl 1-((S)-2-hydroxy-2-(4-((Z)—N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidine-3-carboxylate, Preparation 14B (100 mg, 0.298 mmol) was added. After 2 hours, 1M TBAF in THF (298 μL, 0.298 mmol) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with H2O. The organic layer was dried with MgSO4, filtered, and concentrated. The resulting material was purified on a silica gel cartridge using an EtOAc/hexanes gradient to yield 67 mg of (S)-ethyl 1-((S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate. MS (m+1)=557. HPLC Peak RT=3.32 minutes (Analytical Method A).

Workup

  1. additionwas added
  2. washwashed with H2O
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting material was purified on a silica gel cartridge

Sources & evidence

ORD record
ord-b8f39694d9be431d9dc45ce3d66d08ee
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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