4-Fluorobenzaldehyde → HCID 86672712, compound

HRID 2168535Notes

Reaction equation

HRID 2168535 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) δ7.97 (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-989bacbb3a054c199487ebdb40596389
Source dataset
uspto-grants-2015_06
Patent number
US09045501B2

Reaction notes

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