Potassium Carbonate → 2-(3,4-Dimethoxy-benzyl)-4-[8-(1-phenyl-ethyl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-isoindole-1,3-dione

HRID 216013Notes

Reaction equation

HRID 216013 reaction equation
[CH2:1]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][N:11]([C:16]1[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=1[C:18](=[O:37])[N:19]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=1)[C:20]3=[O:25])[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH:39](C1C=CC=CC=1)C.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.[Pd]>[CH3:36][O:35][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][C:30]=1[O:33][CH3:34])[CH2:26][N:19]1[C:18](=[O:37])[C:17]2[C:21](=[CH:22][CH:23]=[CH:24][C:16]=2[N:11]2[CH2:10][CH:9]3[N:8]([CH:1]([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH3:39])[CH:13]([CH2:14][CH2:15]3)[CH2:12]2)[C:20]1=[O:25]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11454(1-Bromoethyl)benzeneHCID 236274934-(8-Benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione

Product 1

HCID 582958642-(3,4-Dimethoxy-benzyl)-4-[8-(1-phenyl-ethyl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-isoindole-1,3-dioneYield 38.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Compound 7 (50 mg, 0.10 mmol) was hydrogenated (50 psi H2) with 10% Pd/C (5 mg) in EtOAc (1.0 mL) for 5 h. The mixture was filtered through Celite®, and concentrated in vacuo. The crude oil was dissolved in THF (0.4 mL). A portion of 1-bromoethylbenzene (0.03 mL, 0.22 mmol) and K2CO3 (36 mg, 0.26 mmol) were added. The mixture was heated to 50° C. for 4 h. The mixture was cooled to room temperature, filtered through Celite®, and concentrated in vacuo. The crude oil was purified on a Gilson HPLC with a reversed phase Kromasil column (10μ, 100 Å C18, column length 250×50 mm, gradient 90:10-0:100 H2O:MeCN) to give the 19.7 mg (38%) of the title Compound 32 as a yellow solid.

Workup

  1. customfor 5 h
  2. filtrationThe mixture was filtered through Celite®
  3. concentrationconcentrated in vacuo
  4. dissolutionThe crude oil was dissolved in THF (0.4 mL)
  5. temperatureThe mixture was cooled to room temperature
  6. filtrationfiltered through Celite®
  7. concentrationconcentrated in vacuo
  8. customThe crude oil was purified on a Gilson HPLC with a reversed phase Kromasil column (10μ, 100 Å C18, column length 250×50 mm, gradient 90:10-0:100 H2O:MeCN)

Sources & evidence

ORD record
ord-f0e6c11ef8864cc9b7d437e0729acc89
Source dataset
uspto-grants-2012_06
Patent number
US08193191B2

Reaction notes

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