Pyridine → 5-Benzyloxycarbonylamino-2-(2-methyl-imidazol-1-yl)fluorobenzene

HRID 1582337

Reaction equation

HRID 1582337 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH:13]=[CH:12][N:11]=[C:10]2[CH3:14])=[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]=[CH:12][N:11]=[C:10]2[CH3:14])=[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 218766203-fluoro-4-(2-methyl-1H-imidazol-1-yl)aniline

Product 1

HCID 218766515-Benzyloxycarbonylamino-2-(2-methyl-imidazol-1-yl)fluorobenzeneYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Amino-2-(2-methylimidazol-1-yl)fluorobenzene (34.25 g, 0.179 M) was dissolved in dry dichloromethane (600 ml) under nitrogen, and cooled to −5°. Pyridine (17.7 g, 0.224 M) was added, followed by benzyl chloroformate (33.7 g, 0.197 M) over 20 minutes. The mixture was stirred and the temperature allowed to rise to ambient over 16 hours. Aqueous sodium bicarbonate (5%, 250 ml) was added, the organic layer separated, the aqueous layer re-extracted with dichloromethane (2×300 ml), and combined extracts dried (magnesium sulfate). After filtration and evaporation, the residue was recrystallised from toluene (400 ml) to give title product (54.5 g). NMR (DMSO-d6) δ: 2.13 (s, 3H); 5.18 (s, 2H); 6.89 (s, 1H); 7.17 (s, 1H); 7.41 (overlapping m, 7H); 7.73 (dd, 1H); 10.21 (br, 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 (2×300 ml)
  4. dry with materialdried (magnesium sulfate)
  5. filtrationAfter filtration and evaporation
  6. customthe residue was recrystallised from toluene (400 ml)

Sources & evidence

ORD record
ord-71348f1e773d4121a09a5c5e9061104a
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Linked notes

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