1,2-Dichloroethane → benzyl 3-(1-methyl-1H-benzimidazol-2-yl)azetidine-1-carboxylate

HRID 1486754Notes

Reaction equation

HRID 1486754 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH:13]([C:15](O)=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:18][NH:19][C:20]1[C:21]([NH2:26])=[CH:22][CH:23]=[CH:24][CH:25]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C1COCC1>[CH3:18][N:19]1[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[N:26]=[C:15]1[CH:13]1[CH2:14][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 78498N-Methyl-o-phenylenediamineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 109882141-[(Benzyloxy)carbonyl]azetidine-3-carboxylic acid

Product 1

HCID 89486757benzyl 3-(1-methyl-1H-benzimidazol-2-yl)azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-2 (3.0 g, 12.75 mmol) was dissolved in THF (64 mL) and N-methylbenzene-1,2-diamine (2.02 g, 16.58 mmol), EDC (2.93 g, 15.30 mmol), HOAt (2.08 g, 15.30 mmol), and Hunig's base (6.7 mL, 38.3 mmol) were added. After stirring for 18 h at room temperature, the reaction solution was concentrated. The residue was then dissolved in acetic acid (30 mL), stirred at room temperature for 2 h, the solvent was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and 5% aqueous NaHCO3. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes) to provide 1-3 as an off-white solid. MS: m/z=322.4 (M+H).

Workup

  1. concentrationthe reaction solution was concentrated
  2. dissolutionThe residue was then dissolved in acetic acid (30 mL)
  3. stirringstirred at room temperature for 2 h
  4. concentrationthe solvent was concentrated under reduced pressure
  5. customThe residue was partitioned between ethyl acetate and 5% aqueous NaHCO3
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-0026ee03b01646d49633d0bdf5de30ea
Source dataset
uspto-grants-2016_08
Patent number
US09428492B2

Reaction notes

Loading…