4-Fluorobenzaldehyde → HCID 86672712, compound

HRID 2369914Notes

Reaction equation

HRID 2369914 reaction equation
[NH2:1][C:2]1[C:3]([NH:12][CH2:13][CH:14]([O:17][CH3:18])[O:15][CH3:16])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].OOS([O-])=O.[K+].[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=1>CN(C=O)C.O>[CH3:16][O:15][CH:14]([O:17][CH3:18])[CH2:13][N:12]1[C:3]2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[CH:11][C:2]=2[N:1]=[C:30]1[C:29]1[CH:32]=[CH:33][C:26]([F:25])=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 23707502Potassium hydroxy sulfiteHCID 66889618HCID 66889618, compound

Product 1

HCID 86672712HCID 86672712, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 3-amino-2-(2,2-dimethoxyethylamino)benzoate (1.0 g, 3.9 mmol) from Step C of Example 13 in DMF (9 mL) and H2O (0.3 mL) were added oxone (1.6 g, 2.6 mmol) and 4-fluorobenzaldehyde (0.5 mL, 4.3 mmol) and the mixture was stirred overnight at room temperature. The reaction mixture was washed with saturated aqueous sodium bicarbonate, re-extracted with methylene chloride, dried (Na2SO4), filtered, and concentrated under reduced pressure to give the crude material which was purified by column chromatography (silica gel, 5% to 100% ethyl acetate in hexanes) to afford methyl 1-(2,2-dimethoxyethyl)-2-(4-fluorophenyl)-1H-benzo[d]imidazole-7-carboxylate (1.1 g, 79%): 1H NMR (500 MHz, CDCl3) δ 7.97 (dd, J=8.0, 1.0 Hz, 1H), 7.80 (dd, J=8.0, 1.0 Hz, 1H), 7.73-7.70 (m, 2H), 7.32 (t, J=8.0 Hz, 1H), 7.24-7.20 (m, 2H), 4.72 (d, J=5.0 Hz, 2H), 4.24 (t, J=5.0 Hz, 1H), 3.94 (s, 3H), 3.38-3.33 (m, 1H), 3.19 (s, 6H); MS (ESI+) m/z 359 (M+H).

Workup

  1. washThe reaction mixture was washed with saturated aqueous sodium bicarbonate
  2. extractionre-extracted with methylene chloride
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude material which
  7. customwas purified by column chromatography (silica gel, 5% to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c9f3f48145384174858e01fe4e705221
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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