Triethylamine → HCID 66835866, compound

HRID 2277109Notes

Reaction equation

HRID 2277109 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[F:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([C:15]3[CH:16]=[CH:17][C:12]([F:11])=[CH:13][CH:14]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 2856454-Fluorophenylboronic acidHCID 112525844-Bromo-1H-benzimidazole

Product 1

HCID 66835866HCID 66835866, compoundYield 15.6%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A round bottom flask charged with molecular sieves, 4A (189 mg, 1.918 mmol) was flame-dried, then allowed to cool to room temperature. To this vial were added 4-bromo-1H-benzo[d]imidazole (0.378 g, 1.918 mmol), copper (II) acetate (0.523 g, 2.88 mmol), and 4-fluorophenylboronic acid (0.805 g, 5.76 mmol) followed by CH2Cl2 (Volume: 9.59 ml) and triethylamine (0.695 ml, 4.99 mmol). The heterogeneous green reaction was stirred at room temperature. After 19 h, the reaction mixture was filtered through a disposable filter funnel and the filter cake rinsed with CH2Cl2. The filtrate was concentrated to afford a green residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (24 g column, 35 mL/min, 0-100% EtOAc in hexanes over 25 min, tr=13 min) gave 4-bromo-1-(4-fluorophenyl)-1H-benzo[d]imidazole (158 mg, 0.299 mmol, 15.56% yield) as a white solid. LC-MS showed by-product was present. The material was re-dissolved in a minimal amount of CH2Cl2 (required a few drops of MeOH). Purification of the crude material by silica gel chromatography using an ISCO machine (12 g column, 30 mL/min, 0-25% EtOAc in hexanes over 13 min, tr=10 min) gave Preparation 47A (158 mg, 0.299 mmol, 15.56% yield) as a white solid. LC-MS showed the product was 55% pure. The mixture was further purified by MPLC (40 g column, 36 mL/min, 30-60% EtOAc in hexanes) to afford Preparation 47A as a white solid (51 mg, 9.1%). MS (ESI): m/z=291.0 [M+H]+. HPLC Peak tr=1.70 minutes was product. HPLC conditions: Column:Luna C18 4.6×30 mm 3u A:10:90 H2O:ACN NH4OAc/B:10:90 H2O:ACN NH4OAc; 0%-95% B in 2 min; 4 mL/min flow.

Workup

  1. customwas flame-dried
  2. customThe heterogeneous green reaction
  3. filtrationthe reaction mixture was filtered through a disposable filter funnel
  4. washthe filter cake rinsed with CH2Cl2
  5. concentrationThe filtrate was concentrated
  6. customto afford a green residue
  7. customto be chromatographed
  8. customPurification of the crude material by silica gel chromatography
  9. customan ISCO machine (24 g column, 35 mL/min, 0-100% EtOAc in hexanes over 25 min, tr=13 min)

Sources & evidence

ORD record
ord-5d69a88003284feca5a3202eb6cb56b0
Source dataset
uspto-grants-2015_09
Patent number
US09133160B2

Reaction notes

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