Tetrahydrofuran → HCID 66955235, compound

HRID 1948525Notes

Reaction equation

HRID 1948525 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.CCN(C(C)C)C(C)C.[OH:28][CH:29]([C:43]1[CH:48]=[CH:47][C:46](/[C:49](=[N:51]/O)/[NH2:50])=[CH:45][CH:44]=1)[CH2:30][N:31]1[CH2:36][CH2:35][CH2:34][C@H:33]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:32]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C(#N)C.C(OCC)(=O)C>[OH:28][CH:29]([C:43]1[CH:48]=[CH:47][C:46]([C:49]2[N:51]=[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:50]=2)=[CH:45][CH:44]=1)[CH2:30][N:31]1[CH2:36][CH2:35][CH2:34][C@H:33]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:32]1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 58374105HCID 58374105, compoundHCID 87214058HCID 87214058, compound

Product 1

HCID 66955235HCID 66955235, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride, Int-II-D (150 mg, 0.58 mmol) was dissolved in acetonitrile (10 mL) and DIEA (0.185 mL, 1.061 mmol) and ethyl 2-((3R)-1-(2-hydroxy-2-(4-((Z)—N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidin-3-yl)acetate (185 mg, 0.530 mmol) were added. After one hr, TBAF in THF (0.530 mL, 0.530 mmol) was added and the reaction mixture was stirred overnight at room temperature. LCMS shows two new peaks. One is the desired mass and the other has a much higher mass which corresponds to double addition of acid fluoride. The reaction mixture was diluted with ethyl acetate and washed with saturated NaCl. The organic layer was dried with MgSO4, filtered, and concentrated. Solids were purified by a silica gel cartridge using an EtOAc/hexanes gradient to yield 72 mgs of ethyl 2-((3R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetate. MS (m+1)=571. HPLC Peak RT=3.39 minutes.

Workup

  1. washwashed with saturated NaCl
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customSolids were purified by a silica gel cartridge

Sources & evidence

ORD record
ord-fc763b1c63464962a4339133fbb7db1f
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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