Trimethylaluminum → 2-Cyclohexyl-N-(2,6-dichloro-4-methoxy-benzyl)-4-hydroxy-butyramide

HRID 1670815Notes

Reaction equation

HRID 1670815 reaction equation
Cl.[Cl:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([Cl:13])[C:4]=1[CH2:5][NH2:6].C[Al](C)C.[CH:18]1([CH:24]2[CH2:28][CH2:27][O:26][C:25]2=[O:29])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C1(C)C=CC=CC=1>[CH:18]1([CH:24]([CH2:28][CH2:27][OH:26])[C:25]([NH:6][CH2:5][C:4]2[C:3]([Cl:2])=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=2[Cl:13])=[O:29])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 220132343-Cyclohexyl-dihydro-furan-2-oneHCID 673555502,6-Dichloro-4-methoxy-benzylamine hydrochloride

Product 1

HCID 673553892-Cyclohexyl-N-(2,6-dichloro-4-methoxy-benzyl)-4-hydroxy-butyramideYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Treat a mixture of 2,6-dichloro-4-methoxy-benzylamine hydrochloride (4.0 g, 16.6 mmol) and toluene (100 mL) with trimethylaluminum (2 M in toluene, 16.6 mL, 33.2 mmol) at room temperature for 10 minutes. To the mixture, add a solution of 3-cyclohexyl-dihydro-furan-2-one (2.51 g, 14.94 mmol) in toluene (50 mL). Stir the reaction at reflux for 6 hours. Cool the reaction and quench with HCl (1 N, 50 mL). Partition the mixture with ethyl acetate and HCl (1 N). Separate the organic layer and wash with water and brine. After drying the organic layer over sodium sulfate and filtration, concentrate the filtrate to afford 4.5 g (81%) of the title compound as white solid. MS (m/z): 374 (M+H)+.

Workup

  1. additionTreat
  2. customthe reaction
  3. temperatureat reflux for 6 hours
  4. temperatureCool
  5. customthe reaction
  6. customquench with HCl (1 N, 50 mL)
  7. customPartition the mixture with ethyl acetate and HCl (1 N)
  8. customSeparate the organic layer
  9. washwash with water and brine
  10. customAfter drying the organic layer
  11. filtrationover sodium sulfate and filtration
  12. concentrationconcentrate the filtrate

Sources & evidence

ORD record
ord-46e41cf7cff54f5c91cbe6e85cd6fc8c
Source dataset
uspto-grants-2011_08
Patent number
US07994176B2

Reaction notes

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