Pyridine → 5-Benzyloxycarbonylamino-2-(4-methylimidazol-1-yl)fluorobenzene

HRID 1582341

Reaction equation

HRID 1582341 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]2)=[C:6]([F:8])[CH:7]=1.N1C=CC=CC=1.Cl[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23].C(=O)(O)[O-].[Na+]>ClCCl>[CH2:25]([O:24][C:22]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]2)=[C:6]([F:8])[CH:7]=1)=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 218766383-Fluoro-4-(4-methyl-1H-imidazol-1-yl)aniline

Product 1

HCID 218766725-Benzyloxycarbonylamino-2-(4-methylimidazol-1-yl)fluorobenzeneYield 92.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Amino-2-(4-methylimidazol-1-yl)fluorobenzene (50.6 g, 0.265 M) was dissolved in dry dichloromethane (800 ml) under nitrogen, and cooled to −5°. Pyridine (26.1 g, 0.33 M) was added, followed by benzyl chloroformate (49.9 g, 0.292 M) over 30 minutes. The mixture was stirred and the temperature allowed to rise to ambient over 16 hours. Aqueous sodium bicarbonate (5%, 350 ml) was added, the organic layer separated, and the aqueous layer re-extracted with dichloromethane (2×200 ml), and combined organics dried (magnesium sulfate). After filtration and evaporation, the residue was recrystallised from toluene (300 ml) to give title product (80 g). NMR (DMSO-d6) δ: 2.15 (s, 3H); 5.16 (s, 2H); 7.13 (s, 1H); 7.31 (dd, 1H); 7.41 (m, 5H); 7.48 (t, 1H); 7.57 (dd, 1H); 7.78 (s, 1H); 10.15 (br s, 1H). MS (ESP): 326 (MH+) for C18H16FN3O2

Workup

  1. temperaturecooled to −5°
  2. customthe organic layer separated
  3. extractionthe aqueous layer re-extracted with dichloromethane (2×200 ml)
  4. dry with materialcombined organics dried (magnesium sulfate)
  5. filtrationAfter filtration and evaporation
  6. customthe residue was recrystallised from toluene (300 ml)

Sources & evidence

ORD record
ord-449d5b981ccd430f90c711eb19cd3669
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Linked notes

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