Sodium Carbonate → 1-(2-Chlorophenyl)-2-(4-hydroxyphenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-4-one

HRID 2102858Notes

Reaction equation

HRID 2102858 reaction equation
Br[C:2]1[N:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[C:9]2[CH2:8][CH2:7][N:6]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[C:5](=[O:24])[C:4]=2[C:3]=1[CH3:25].[OH:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[Cl:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[N:10]1[C:9]2[CH2:8][CH2:7][N:6]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[C:5](=[O:24])[C:4]=2[C:3]([CH3:25])=[C:2]1[C:30]1[CH:31]=[CH:32][C:27]([OH:26])=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 668652252-Bromo-1-(2-chlorophenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-4-one

Product 1

HCID 166661641-(2-Chlorophenyl)-2-(4-hydroxyphenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-4-oneYield 55.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

2-Bromo-1-(2-chlorophenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-4-one (0.92 g, 2.25 mmol), 4-hydroxyphenylboronic acid (0.35 g, 2.50 mmol) and tetrakis(triphenylphosphine)palladium(0) (350 mg) were dissolved in DME (46 ml) and 1 M Na2CO3 (12 ml)). The resulting solution was degassed and heated at 60° C. under nitrogen overnight. Water and EtOAc were added after cooling and the aqueous phase extracted with EtOAc (×3). The combined organic extracts were dried (Na2SO4), filtered and concentrated to give a crude product that was purified by flash chromatography (heptane:EtOAc gradient) to afford 0.54 g (55%) of the product as a pale yellow solid.

Workup

  1. customThe resulting solution was degassed
  2. additionWater and EtOAc were added
  3. temperatureafter cooling
  4. extractionthe aqueous phase extracted with EtOAc (×3)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude product that
  9. customwas purified by flash chromatography (heptane:EtOAc gradient)

Sources & evidence

ORD record
ord-f4f9e62750784eebb22ac3afb2f37e40
Source dataset
uspto-grants-2009_08
Patent number
US07576095B2

Reaction notes

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