Tetrahydrofuran → 3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol

HRID 1157097Notes

Reaction equation

HRID 1157097 reaction equation
[N+:1]([C:4]1[N:5]([CH2:9][C:10]#[CH:11])[CH:6]=[CH:7][N:8]=1)([O-:3])=[O:2].[N:12]([CH:15]([CH2:18][F:19])[CH2:16][OH:17])=[N+:13]=[N-:14].C1COCC1.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CC(O)(C)C.O>[F:19][CH2:18][CH:15]([N:12]1[CH:11]=[C:10]([CH2:9][N:5]2[CH:6]=[CH:7][N:8]=[C:4]2[N+:1]([O-:3])=[O:2])[N:14]=[N:13]1)[CH2:16][OH:17]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 23667548Sodium AscorbateHCID 546751432-Nitro-1-(prop-2-ynyl)-1H-imidazoleHCID 595110612-Azido-3-fluoropropan-1-ol

Product 1

HCID 595110633-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-olYield 88.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

A solution of 10 (1.9 g, 12.6 mmol) and 29 (1.5 g, 12.6 mmol) in t-BuOH:THF:H2O (22.5 mL, 1:1:1) was treated with CuSO4.5H2O (0.31 g, 1.26 mmol) and sodium ascorbate (0.5 g, 2.52 mmol) and stirred for 1 hr at room temperature. Organic solvents removed under vacuum, the residue dissolved in CH2Cl2 and consecutively washed with H2O, then brine, then dried over MgSO4. The solvent was then concentrated in vacuo and the residue was purified on silica gel using 10% MeOH:CH2Cl2 as the solvent to afford 1 (3.00 g, 88%) as white solid. The product was further purified via recrystallization from EtOAc/hexanes. 1H NMR ((CD3)2CO, 400 MHz) δ: 8.15 (s, 1H), 7.57 (d, J=1.2 Hz, 1H), 7.11 (d, J=1.2 Hz, 1H), 5.79 (s, 2H), 4.87-5.05 (m, 2H), 4.82 (dd, J=4.0, 10.0 Hz, 1H), 4.17-4.45 (m, 1H), 4.03 (t, J=5.6 Hz, 2H). 13C NMR ((CD3)2CO, 100 MHz) δ: 141.8, 127.9, 127.1, 123.5, 83.0, 81.3, 63.0 (d, J=18.69 Hz, 1C), 60.5 (d, J=6.73 Hz, 1C), δ: 44.8; 19F NMR ((CD3)2CO, 376 MHz) 230.2 (ddd, J=19.18, 19.55, 21.60 Hz, IF); Mass Spec (lo-res): Calc'd for C9H11FN6O3: 270.09; found: 271.1 (M+H).

Workup

  1. customOrganic solvents removed under vacuum
  2. dissolutionthe residue dissolved in CH2Cl2
  3. washconsecutively washed with H2O
  4. dry with materialbrine, then dried over MgSO4
  5. concentrationThe solvent was then concentrated in vacuo
  6. customthe residue was purified on silica gel using 10% MeOH

Sources & evidence

ORD record
ord-207314ac3ef546e88a33bc1004aed83e
Source dataset
uspto-grants-2010_10
Patent number
US07807394B2

Reaction notes

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