4-Methylmorpholine → 4-(Allyloxy)-5-bromo-2-chloro-N-methoxy-N-methylbenzamide

HRID 2206679Notes

Reaction equation

HRID 2206679 reaction equation
[CH2:1]([O:4][C:5]1[C:13]([Br:14])=[CH:12][C:8]([C:9]([OH:11])=O)=[C:7]([Cl:15])[CH:6]=1)[CH:2]=[CH2:3].Cl.[CH3:17][NH:18][O:19][CH3:20].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>C(Cl)Cl>[CH2:1]([O:4][C:5]1[C:13]([Br:14])=[CH:12][C:8]([C:9]([N:18]([O:19][CH3:20])[CH3:17])=[O:11])=[C:7]([Cl:15])[CH:6]=1)[CH:2]=[CH2:3]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 533294054-(Allyloxy)-5-bromo-2-chlorobenzoic acid

Product 1

HCID 867140214-(Allyloxy)-5-bromo-2-chloro-N-methoxy-N-methylbenzamideYield 95.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-(allyloxy)-5-bromo-2-chlorobenzoic acid 21 (5.0 g, 17.2 mmol) in CH2Cl2 (50 mL) were added N,O-dimethylhydroxylamine HCl (2.1 g, 20.6 mmol), EDCI (4.9 g, 25.8 mmol), HOBT (4.7 g, 34.4 mmol) and NMM (9.5 mL, 86.0 mmol). The reaction mixture was stirred at rt for 15 hours and evaporated in vacuo to remove volatiles. The mixture was extracted with EtOAc/H2O (100 mL/100 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was triturated with hexane (100 mL) and stirred at r.t. for 30 min. The solid was precipitated, filtered, washed with hexane (50 mL) and dried under high vacuum to obtain the desired product (5.5 g, 95%).

Workup

  1. customevaporated in vacuo
  2. customto remove volatiles
  3. extractionThe mixture was extracted with EtOAc/H2O (100 mL/100 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was triturated with hexane (100 mL)
  8. stirringstirred at r.t. for 30 min
  9. customThe solid was precipitated
  10. filtrationfiltered
  11. washwashed with hexane (50 mL)
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-3499d5d413654422999c07fb32d618cf
Source dataset
uspto-grants-2016_06
Patent number
US09371303B2

Reaction notes

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