Water → Methyl 1-isobutyl-8-[4-(2-propoxyethoxy)phenyl]-1,2,3,4-tetrahydro-1-benzazocine-5-carboxylate

HRID 1810803Notes

Reaction equation

HRID 1810803 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:11][CH2:10][CH2:9][C:8]([C:17]([O:19][CH3:20])=[O:18])=[CH:7][C:6]=2[CH:21]=1.[CH2:22]([O:26][CH2:27][CH2:28][O:29][C:30]1[CH:35]=[CH:34][C:33](OB(O)O)=[CH:32][CH:31]=1)[CH2:23][CH2:24]C.C(=O)([O-])[O-].[K+].[K+].O>C1(C)C(CCO)=CC=CC=1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:13]([N:12]1[C:5]2[CH:4]=[CH:3][C:2]([C:33]3[CH:34]=[CH:35][C:30]([O:29][CH2:28][CH2:27][O:26][CH2:22][CH2:23][CH3:24])=[CH:31][CH:32]=3)=[CH:21][C:6]=2[CH:7]=[C:8]([C:17]([O:19][CH3:20])=[O:18])[CH2:9][CH2:10][CH2:11]1)[CH:14]([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 230910874-(2-Butoxyethoxy)phenylboric acidHCID 68539084Methyl 8-bromo-1-(2-methylpropyl)-1,2,3,4-tetrahydro-1-benzazocine-5-carboxylate

Product 1

HCID 68650210Methyl 1-isobutyl-8-[4-(2-propoxyethoxy)phenyl]-1,2,3,4-tetrahydro-1-benzazocine-5-carboxylateYield 72%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 66602552Toluene-ethanol waterSolvent

Procedure

Under argon atmosphere, a mixture of methyl 8-bromo-1-isobutyl-1,2,3,4-tetrahydro-1-benzazocine-5-carboxylate (1.3 g), 4-(2-butoxyethoxy)phenyl boric acid (1.07 g) and potassium carbonate (1.02 g) in toluene-ethanol-water (40-4-4 ml) was stirred at room temperature for 1 hour. To the reaction system was added tetrakis(triphenylphosphine)-palladium (0.21 g), and the mixture was refluxed for 5 hours. After cooling 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. After concentration under reduced pressure, the residue was separated to purify by column chromatography (ethyl acetate:hexane=1:49→1:19→1:9) to give methyl 1-isobutyl-8-[4-(2-propoxyethoxy)phenyl]-1,2,3,4-tetrahydro-1-benzazocine-5-carboxylate (1.20 g) as a yellow oily material.

Workup

  1. temperaturethe mixture was refluxed for 5 hours
  2. temperatureAfter cooling 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. concentrationAfter concentration under reduced pressure
  7. customthe residue was separated
  8. customto purify by column chromatography (ethyl acetate:hexane=1:49→1:19→1:9)

Sources & evidence

ORD record
ord-a2a6368651b740429e3539c8ef05ba88
Source dataset
uspto-grants-2013_01
Patent number
US08362058B2

Reaction notes

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