Potassium Carbonate → methyl 9-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-2,3,4,5-tetrahydro-1H-1-benzoazonin-6-carboxylate

HRID 402285Notes

Reaction equation

HRID 402285 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:12][CH2:11][CH2:10][CH2:9][C:8]([C:18]([O:20][CH3:21])=[O:19])=[CH:7][C:6]=2[CH:22]=1.[CH2:23]([O:27][CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34](OB(O)O)=[CH:33][CH:32]=1)[CH2:24][CH2:25][CH3:26].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:23]([O:27][CH2:28][CH2:29][O:30][C:31]1[CH:32]=[CH:33][C:34]([C:2]2[CH:3]=[CH:4][C:5]3[N:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:12][CH2:11][CH2:10][CH2:9][C:8]([C:18]([O:20][CH3:21])=[O:19])=[CH:7][C:6]=3[CH:22]=2)=[CH:35][CH:36]=1)[CH2:24][CH2:25][CH3:26]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 230910874-(2-Butoxyethoxy)phenylboric acidHCID 68650366methyl 9-bromo-1-isobutyl-2,3,4,5-tetrahydro-1H-1-benzoazonin-6-carboxylate

Product 1

HCID 68649753methyl 9-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-2,3,4,5-tetrahydro-1H-1-benzoazonin-6-carboxylateYield 98.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

A suspension of methyl 9-bromo-1-isobutyl-2,3,4,5-tetrahydro-1H-1-benzoazonin-6-carboxylate (2.1 g) and 4-(2-butoxyethoxy)phenyl boric acid (1.77 g) and potassium carbonate (2.06 g) in toluene (25 ml), ethanol (2.5 ml) and water (2.5 ml) was stirred under argon atmosphere for 1 hour, and then tetrakis(triphenylphosphine)palladium (332 mg) was added. The mixture was refluxed for 5 hours. After returning to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1→hexane:ethyl acetate=9:1) to give methyl 9-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-2,3,4,5-tetrahydro-1H-1-benzoazonin-6-carboxylate (2.7 g) as a yellow oily material.

Workup

  1. temperatureThe mixture was refluxed for 5 hours
  2. customAfter returning to room temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1→hexane:ethyl acetate=9:1)

Sources & evidence

ORD record
ord-56ffb642255b4c63a120741e98bf3443
Source dataset
uspto-grants-2014_06
Patent number
US08741943B2

Reaction notes

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