Tetrahydrofuran → 7-fluoro-6-methoxy-1-methyl-1,3-dihydro-2H-benzimidazol-2-one

HRID 882205Notes

Reaction equation

HRID 882205 reaction equation
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=C(N)C=1NC.C1N=CN([C:18]([N:20]2[CH:24]=[N:23][CH:22]=[CH:21]2)=O)C=1.C1C[O:28]CC1>>[F:1][C:2]1[C:21]2[N:20]([CH3:18])[C:24](=[O:28])[NH:23][C:22]=2[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 682631,1'-CarbonyldiimidazoleHCID 667491243-fluoro-4-methoxy-N2-methylbenzene-1,2-diamine

Product 1

HCID 866861057-fluoro-6-methoxy-1-methyl-1,3-dihydro-2H-benzimidazol-2-one

Procedure

3-fluoro-4-methoxy-N2-methylbenzene-1,2-diamine (7-3, 1.09 g, 6.40 mmol) was dissolved in anhydrous THF (15 ml) and treated with CDI (1.25 g, 7.69 mmol, 1.2 eq). The resulting orange solution was stirred at reflux for 6 h, then cooled to 23 deg C. The remaining dark reaction mixture was partitioned between EtOAc (2×40 ml) and water (45 ml). The combined organic layers were dried over Na2SO4 and concentrated. The crude mixture was purified via flash column chromatography (SiO2: 100% Hex to 50:50 Hex:EtOAc), affording the title compound, 7-fluoro-6-methoxy-1-methyl-1,3-dihydro-2H-benzimidazol-2-one (7-4), as a maroon oil. 1H NMR (500 MHz, CDCl3) δ 7.11 (s, 1H), 6.68-6.74 (m, 2H), 3.89 (s, 3H), 3.60 (s, 3H). LRMS m/z: Calc'd for C9H9FN2O2(M+H) 197.2, found 196.9.

Workup

  1. temperatureat reflux for 6 h
  2. temperaturecooled to 23 deg C
  3. customThe remaining dark reaction mixture
  4. customwas partitioned between EtOAc (2×40 ml) and water (45 ml)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude mixture was purified via flash column chromatography (SiO2: 100% Hex to 50:50 Hex:EtOAc)

Sources & evidence

ORD record
ord-0c4d1002fad342fa9ad9b68c8ef6def3
Source dataset
uspto-grants-2015_03
Patent number
US08993779B2

Reaction notes

Loading…