Tetrahydrofuran → N-[4-(1,4-Dioxa-8-azaspiro[4.5]dec-8-yl)benzyl]-N-hydroxyurea

HRID 1061226Notes

Reaction equation

HRID 1061226 reaction equation
C[Si]([N:5]=[C:6]=[O:7])(C)C.[OH:8][NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:26][CH2:25][C:20]3([O:24][CH2:23][CH2:22][O:21]3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1.C1COCC1.O1CCOCC1>O>[O:21]1[C:20]2([CH2:19][CH2:18][N:17]([C:14]3[CH:15]=[CH:16][C:11]([CH2:10][N:9]([OH:8])[C:6]([NH2:5])=[O:7])=[CH:12][CH:13]=3)[CH2:26][CH2:25]2)[O:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 312751,4-DioxaneHCID 70696Trimethylsilyl isocyanateHCID 129659608-{4-[(Hydroxyamino)methyl]phenyl]-1,4-dioxa-8-azaspiro[4.5]decane

Product 1

HCID 12965961N-[4-(1,4-Dioxa-8-azaspiro[4.5]dec-8-yl)benzyl]-N-hydroxyureaYield 73%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Trimethylsilyl isocyanate (2.1 mL, 14.85 mmol) was added dropwise into a mixture of 8-{4-[(hydroxyamino)methyl]phenyl}-1,4-dioxa-8-azaspiro[4.5]decane (2.61 g, 9.9 mmol) (which was obtained in Example 52), THF (20 mL) and dioxane (20 mL). The mixture was stirred at room temperature for 24 hours, poured into water and extracted with ethyl acetate. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexanes/ethyl acetate/methyl alcohol 10/5/1) gave a white solid (2.2 g, 73% yield); mp 153-154° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.70 (m, 4H), 3.21 (m, 4H), 3.89 (s, 4H), 4.37 (s, 2H), 6.23 (brs, 2H), 6.86 (m, 2H), 7.10 (m, 2H), 9.19 (s, 1H); MS (ES) m/z: 308 (MH+); Anal. Calcd. for C15H21N3O4: C, 58.62; H, 6.89; N, 13.67. Found: C, 58.37; H, 6.78; N, 13.47

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic extracts were dried over MgSO4
  3. customEvaporation and purification by flash chromatography (hexanes/ethyl acetate/methyl alcohol 10/5/1)

Sources & evidence

ORD record
ord-b03eeefcbbb34d449b615562c651de1a
Source dataset
uspto-grants-2003_02
Patent number
US06525202B2

Reaction notes

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