Dimethylformamide → HCID 86677811, compound

HRID 1499889Notes

Reaction equation

HRID 1499889 reaction equation
CN(C)C=O.N1C(Cl)=NC(Cl)=NC=1[Cl:8].[Cl:15][C:16]1[C:21]([Cl:22])=[CH:20][C:19]([CH:23](O)[CH3:24])=[C:18]([O:26][CH3:27])[C:17]=1[CH:28]1[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]1>C(Cl)Cl.O>[Cl:15][C:16]1[C:21]([Cl:22])=[CH:20][C:19]([CH:23]([Cl:8])[CH3:24])=[C:18]([O:26][CH3:27])[C:17]=1[CH:28]1[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]1

Participants

6

Reactant 3

HCID 6228Dimethylformamide4×HCID 7954Cyanuric chlorideHCID 86677812HCID 86677812, compound

Product 1

HCID 86677811HCID 86677811, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

N,N-Dimethylformamide (0.92 mL, 12 mmol) was added to solid cyanuric chloride (2.2 g, 12 mmol) at room temperature (DMF is absorbed by the solid). The mixture was allowed to stand for 10 min, treated with methylene chloride (60 mL), and stirred for a few minutes to break up the solid. The reaction mixture was treated with a solution of tert-butyl 3-[2,3-dichloro-5-(1-hydroxyethyl)-6-methoxyphenyl]azetidine-1-carboxylate (3.0 g, 8.0 mmol) in methylene chloride (30 mL) and stirred at 35-40° C. for 2 h. The reaction mixture was treated with additional N,N-dimethylformamide (1 mL) and stirred at 35-40° C. for 4 h. The reaction required another treatment of N,N-dimethylformamide (1 mL) with stirring at 35-40° C. overnight to proceed to completion. The reaction mixture was diluted with water and dichloromethane. The organic phase was separated and washed with saturated sodium bicarbonate solution, water and brine, dried over magnesium sulfate, filtered, and concentrated to a crude residue. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (5%-40%) to give the desired product (2.8 g, 90%). LCMS for C13H15Cl3NO3 ([M-(t-Bu)+H]+H)+: m/z=338.0, 340.0; Found: 337.9, 339.9.

Workup

  1. customis absorbed by the solid)
  2. additiontreated with methylene chloride (60 mL)
  3. stirringstirred at 35-40° C. for 2 h
  4. stirringstirred at 35-40° C. for 4 h
  5. customThe reaction
  6. stirringwith stirring at 35-40° C. overnight
  7. customThe organic phase was separated
  8. washwashed with saturated sodium bicarbonate solution, water and brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to a crude residue
  12. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-43b4d14e23e1401da510b7aabd658436
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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