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

HRID 254339Notes

Reaction equation

HRID 254339 reaction equation
Br[C:2]1[N:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[C:9]2[CH2:8][CH2:7][N:6]([N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[C:5](=[O:25])[C:4]=2[C:3]=1[CH3:26].[OH:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=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:18][C:12]1[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=1[N:10]1[C:9]2[CH2:8][CH2:7][N:6]([N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[C:5](=[O:25])[C:4]=2[C:3]([CH3:26])=[C:2]1[C:31]1[CH:32]=[CH:33][C:28]([OH:27])=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 220384662-Bromo-1-(2,4-Dichlorophenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-4-one

Product 1

HCID 166661651-(2,4-Dichlorophenyl)-2-(4-hydroxyphenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-4-oneYield 87%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

2-Bromo-1-(2,4-Dichlorophenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-4-one (450 mg, 0.98 mmol), 4-hydroxyphenylboronic acid (150 mg, 1.09 mmol) and tetrakis(triphenylphosphine)palladium(0) (150 mg) were dissolved in DME (20 ml) and 1 M Na2CO3 (5 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 0.40 g (87%) 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-ced9feb57832421bbc113e60dd42baf2
Source dataset
uspto-grants-2011_01
Patent number
US07875626B2

Reaction notes

Loading…