Triethylamine → HCID 86636418, compound

HRID 1471492Notes

Reaction equation

HRID 1471492 reaction equation
[Br:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=2CO)=[CH:4][C:3]=1[CH2:19][O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1.[CH2:27]([N:29]([CH2:32]C)CC)C.CS(Cl)(=O)=[O:36].C(OCC)(=O)C.O>ClCCl.CN(C)C=O>[Br:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=2[CH2:27][NH:29][CH:32]=[O:36])=[CH:4][C:3]=1[CH2:19][O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 22728543Water ethylacetateHCID 67441871HCID 67441871, compound

Product 1

HCID 86636418HCID 86636418, compoundYield 68.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[4-bromo-3-(2-tetrahydropyranyloxymethyl)phenoxy]-3-(hydroxymethyl)benzonitrile (12.1 g, 28.9 mmol) in dichloromethane (100 mL) were added triethylamine (8.0 mL, 58 mmol) and methanesulfonyl chloride (2.5 mL, 32 mmol) at 0° C., and the mixture was stirred at room temperature for 1 h. The mixture was washed with water and brine, and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. To a solution of the residue in N,N-dimethylformamide (100 mL) was added sodium diformylimide (3.29 g, 34.7 mmol), and the mixture was stirred at 50° C. for 2 h. The mixture was poured into ethyl acetate/water. The organic layer was washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. To a solution of the residue in 1,4-dioxane (80 mL) was added 3 M NaOH (10 mL), and the mixture was stirred at room temperature for 1 h. The mixture was poured into ethyl acetate/water. The organic layer was washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column (5:5 to 4:6 hexane/ethyl acetate) to give 4-[4-bromo-3-(2-tetrahydropyranyloxymethyl)phenoxy]-3-(formylaminomethyl)benzonitrile (8.77 g, 68%).

Workup

  1. washThe mixture was washed with water and brine
  2. dry with materialdried on anhydrous sodium sulfate
  3. customThe solvent was removed under reduced pressure
  4. stirringthe mixture was stirred at 50° C. for 2 h
  5. washThe organic layer was washed with brine
  6. dry with materialdried on anhydrous sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. additionTo a solution of the residue in 1,4-dioxane (80 mL) was added 3 M NaOH (10 mL)
  9. stirringthe mixture was stirred at room temperature for 1 h
  10. additionThe mixture was poured into ethyl acetate/water
  11. washThe organic layer was washed with brine
  12. dry with materialdried on anhydrous sodium sulfate
  13. customThe solvent was removed under reduced pressure
  14. customThe residue was purified by silica gel column (5:5 to 4:6 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-62edb933dddf4c42a5682e67b9604389
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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