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

HRID 2202815Notes

Reaction equation

HRID 2202815 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-carboxylateYield 81%

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 hours at ambient temperature, the reaction solution was concentrated. The residue was then dissolved in acetic acid (30 mL). After stirring at ambient temperature for 2 hours, the solvent was removed. The residue was partitioned between ethyl acetate and 5% aqueous NaHCO3. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography (EtOAc/Hexanes) to provide 1-3 as a off-white solid (3.32 g, 81%). 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. stirringAfter stirring at ambient temperature for 2 hours
  4. customthe solvent was removed
  5. customThe residue was partitioned between ethyl acetate and 5% aqueous NaHCO3
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-fe9af9f8e4454b06ace50e8e633827a0
Source dataset
uspto-grants-2016_06
Patent number
US09365562B2

Reaction notes

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