Dimethylacetamide → Benzimidazole

Temperature

120 °C

Aldehyde 1e (2.05 g, 4.28 mmol), 1,2-diamino-3,5-difluorobenzene (617 mg, 4.28 mmol) and sodium bisulfite (891 mg, 8.57 mmol) were dissolved in N,N-dimethylacetamide (43 mL) and heated in a 120° C. oilbath for 21 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (100 mL) and washed with half-saturated aqueous sodium chloride solution (75 mL, a 1:1 mixture of deionized water and saturated aqueous sodium chloride solution). The aqueous layer was back-extracted with ethyl acetate (2×100 mL). All the organic extracts were combined, dried over magnesium sulfate, and concentrated to a brown tar (3.39 g). This crude material was purified by silica gel chromatography (eluting with a gradient of 70% to 100% ethyl acetate in hexanes), to give benzoimidazole product 1f (2.11 g, 81%) as a tan foam: 1H NMR (CD3OD) δ 8.46 (s, 1H), 8.41 (s, 1H), 8.29 (s, 1H), 7.87 (d, J=8.6 Hz, 1H), 7.46 (dd, J=1.3, 8.6 Hz, 1H), 7.13 (m, 1H), 6.84 (m, 1H), 5.99 (dd, J=2.3, 9.9 Hz, 1H), 4.60 (s, 2H), 4.01 (m, 1H), 3.86 (m, 1H), 3.32 (m, 2H, obscured by solvent peak) 2.67 (m, 1H), 2.28 (s, 3H), 2.18 (m, 2H), 1.89 (m, 1H), 1.73 (m, 2H), 1.47 (s, 9H), 1.13 (t, J=7.1 Hz, 1H). Anal. (C33H36F2N6O3.0.4 H2O) C, H, N, F.

1. temperatureAfter cooling to room temperature
2. washwashed with half-saturated aqueous sodium chloride solution (75 mL
3. additiona 1:1 mixture of deionized water and saturated aqueous sodium chloride solution)
4. extractionThe aqueous layer was back-extracted with ethyl acetate (2×100 mL)
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated to a brown tar (3.39 g)
7. customThis crude material was purified by silica gel chromatography (
8. washeluting with a gradient of 70% to 100% ethyl acetate in hexanes),

ORD record

ord-1681d3029de64524bcfb59f48b5642e4

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07008953B2