1,2-Dichloroethane → HCID 67459028, compound

HRID 1804474Notes

Reaction equation

HRID 1804474 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([OH:14])=O)[C:8]=2[CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(Cl)CCl.O/[N:45]=[C:46](/[C:48]1[CH:65]=[CH:64][C:51]([CH2:52][N:53]2[CH2:56][CH:55]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:54]2)=[CH:50][CH:49]=1)\[NH2:47].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>C(#N)C>[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:14][N:47]=[C:46]([C:48]4[CH:49]=[CH:50][C:51]([CH2:52][N:53]5[CH2:54][CH:55]([C:57]([O:59][C:60]([CH3:61])([CH3:63])[CH3:62])=[O:58])[CH2:56]5)=[CH:64][CH:65]=4)[N:45]=3)[C:8]=2[CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 7

HCID 111,2-DichloroethaneHCID 8028TetrahydrofuranHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 58504340HCID 58504340, compoundHCID 67455256HCID 67455256, compound

Product 1

HCID 67459028HCID 67459028, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 5-phenyl-4-(3,3,3-trifluoropropyl)isoxazole-3-carboxylic acid (5 mg, 0.018 mmol), HOBt (4.83 mg, 0.032 mmol) and diisopropylethylamine (12.3 μL, 0.070 mmol) in acetonitrile (0.5 mL) was added EDC (7.90 mg, 0.041 mmol) and (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Int.1, 5.35 mg, 0.018 mmol). The reaction mixture was stirred at 23° C. for 2.5 h. The mixture was concentrated, and the residue was diluted with ethyl acetate (3 mL), washed with a saturated aqueous solution of sodium bicarbonate (1 mL), washed with water (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. The mixture was concentrated and dissolved in acetonitrile (0.5 mL). A 1M solution of tetrabutylammonium fluoride in tetrahydrofuran (35 μL, 0.035 mmol) was added, and the reaction mixture was stirred for 1 h. The reaction mixture was concentrated, and the residue was diluted with ethyl acetate (3 mL), washed with water (1 mL), washed with a saturated aqueous solution of sodium carbonate (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification on a preparative TLC plate with hexanes/ethyl acetate (7/3) afforded tert-butyl 1-(4-(5-(5-phenyl-4-(3,3,3-trifluoropropyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate.

Workup

  1. concentrationThe mixture was concentrated
  2. additionthe residue was diluted with ethyl acetate (3 mL)
  3. washwashed with a saturated aqueous solution of sodium bicarbonate (1 mL)
  4. washwashed with water (1 mL)
  5. washwashed with brine (1 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe mixture was concentrated
  8. dissolutiondissolved in acetonitrile (0.5 mL)
  9. stirringthe reaction mixture was stirred for 1 h
  10. concentrationThe reaction mixture was concentrated
  11. additionthe residue was diluted with ethyl acetate (3 mL)
  12. washwashed with water (1 mL)
  13. washwashed with a saturated aqueous solution of sodium carbonate (1 mL)
  14. washwashed with brine (1 mL)
  15. dry with materialdried over anhydrous sodium sulfate
  16. concentrationConcentration
  17. customfollowed by purification on a preparative TLC plate with hexanes/ethyl acetate (7/3)

Sources & evidence

ORD record
ord-d863276f99434033a738e0a8ba38fb23
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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