2-Chlorobenzaldehyde → HCID 86729960, compound

HRID 2168537Notes

Reaction equation

HRID 2168537 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].[Cl:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH:22]=O>C(Cl)Cl>[Cl:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[C:22]1[N:12]([CH2:13][CH:14]([O:17][CH3:18])[O:15][CH3:16])[C:3]2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[CH:11][C:2]=2[N:1]=1

Participants

4

Reactant 2

HCID 69962-ChlorobenzaldehydeHCID 66889618HCID 66889618, compound

Product 1

HCID 86729960HCID 86729960, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
55 °C

Procedure

Methyl 3-amino-2-(2,2-dimethoxyethylamino)benzoate (498 mg, 2.0 mmol) from Step C of Example 13, 2-chlorobenzaldehyde (303 mg, 2.15 mmol) and 4 {acute over (Å)} molecular sieves were stirred in methylene chloride (6 mL) at room temperature for 1 h. To this mixture was added iodobenzene 1,1-diacetate (1.26 g, 3.92 mmol) and the reaction mixture was heated (external temperature=55° C.) for 10 min. The reaction was quenched with saturated aqueous sodium bicarbonate, 10% aqueous sodium thiosulfate and pH adjusted to 8. The organic phase was extracted with methylene chloride, washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 3:1 hexanes/ethyl acetate) to give methyl 2-(2-chlorophenyl)-1-(2,2-dimethoxyethyl)-1H-benzo[d]imidazole-7-carboxylate as a brown oil (275 mg, 38%): 1H NMR (500 MHz, MeOD) δ 7.91 (d, J=8.0 Hz, 1H), 7.82 (d, J=7.5 Hz, 1H), 7.66-7.60 (m, 3H), 7.56 (d, J=7.5 Hz, 1H), 7.40 (t, J=7.5 Hz, 1H), 4.28 (t, J=4.5 Hz, 1H), 4.27-4.08 (m, 2H), 3.98 (s, 3H), 3.12 (s, 3H), 3.09 (s, 3H); MS (ESI+) m/z 375 (M+H).

Workup

  1. customThe reaction was quenched with saturated aqueous sodium bicarbonate, 10% aqueous sodium thiosulfate
  2. extractionThe organic phase was extracted with methylene chloride
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by column chromatography (silica gel, 3:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-36017ae0d0154bb493390e05b1e9b22a
Source dataset
uspto-grants-2015_06
Patent number
US09045501B2

Reaction notes

Loading…