Tetrahydrofuran → HCID 67459036, compound

HRID 1804484Notes

Reaction equation

HRID 1804484 reaction equation
[F:1][C:2]([C:6]1[C:7]([C:17](F)=[O:18])=[N:8][O:9][C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([F:5])[CH2:3][CH3:4].O/[N:21]=[C:22](/[C:24]1[CH:41]=[CH:40][C:27]([CH2:28][N:29]2[CH2:32][CH:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30]2)=[CH:26][CH:25]=1)\[NH2:23].CCN(C(C)C)C(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>C(#N)C>[F:1][C:2]([C:6]1[C:7]([C:17]2[O:18][N:23]=[C:22]([C:24]3[CH:25]=[CH:26][C:27]([CH2:28][N:29]4[CH2:30][CH:31]([C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])[CH2:32]4)=[CH:40][CH:41]=3)[N:21]=2)=[N:8][O:9][C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([F:5])[CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 58504340HCID 58504340, compoundHCID 58537229HCID 58537229, compound

Product 1

HCID 67459036HCID 67459036, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(1,1-difluoropropyl)-5-phenylisoxazole-3-carbonyl fluoride (7.2 mg, 0.027 mmol) and (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Int.1, 8.17 mg, 0.027 mmol) in acetonitrile (1 mL) was added Hunig's Base (9.34 μL, 0.053 mmol), and the reaction mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated and diluted with ethyl acetate (3 ml), washed with water (1 mL), washed with a saturated aqueous solution of sodium carbonate (1 mL), washed brine (1 mL), and dried over anhydrous sodium sulfate. The mixture was concentrated, dissolved in acetonitrile (1 mL), and a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran (53 μL, 0.053 mmol) was added. The reaction mixture was stirred at room temperature for 5 h. The reaction mixture was concentrated, diluted with ethyl acetate (3 ml), washed with water (1 ml), washed with a saturated aqueous solution of sodium bicarbonate (1 ml), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by preparative HPLC afforded tert-butyl 1-(4-(5-(4-(1,1-difluoropropyl)-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethyl acetate (3 ml)
  3. washwashed with water (1 mL)
  4. washwashed with a saturated aqueous solution of sodium carbonate (1 mL)
  5. washwashed brine (1 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe mixture was concentrated
  8. dissolutiondissolved in acetonitrile (1 mL)
  9. stirringThe reaction mixture was stirred at room temperature for 5 h
  10. concentrationThe reaction mixture was concentrated
  11. additiondiluted with ethyl acetate (3 ml)
  12. washwashed with water (1 ml)
  13. washwashed with a saturated aqueous solution of sodium bicarbonate (1 ml)
  14. washwashed with brine (1 mL)
  15. dry with materialdried over anhydrous sodium sulfate
  16. concentrationConcentration
  17. customfollowed by purification by preparative HPLC

Sources & evidence

ORD record
ord-0b9558e99c784e31bb05d4fba14566a5
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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