Cesium carbonate → (R)-ethyl 5-(3-(benzyloxycarbonylamino)piperidin-1-yl)-8-cyano-9H-carbazole-2-carboxylate

HRID 1811096Notes

Reaction equation

HRID 1811096 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:8]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17]2[C:9]=1[C:10]1[CH:11]=[CH:12][C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:14][C:15]=1[NH:16]2.[NH:28]1[CH2:33][CH2:32][CH2:31][C@@H:30]([NH:34][C:35](=[O:44])[O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:29]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:37]([O:36][C:35]([NH:34][C@@H:30]1[CH2:31][CH2:32][CH2:33][N:28]([C:8]2[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17]3[C:9]=2[C:10]2[CH:11]=[CH:12][C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:14][C:15]=2[NH:16]3)[CH2:29]1)=[O:44])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 1514176Benzyl (3R)-piperidin-3-ylcarbamateHCID 66606406ethyl 5-bromo-8-cyano-9H-carbazole-2-carboxylate

Product 1

HCID 86642946(R)-ethyl 5-(3-(benzyloxycarbonylamino)piperidin-1-yl)-8-cyano-9H-carbazole-2-carboxylateYield 37%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Step 2 A mixture of cesium carbonate (0.960 g, 2.95 mmol), (RS)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.059 g, 0.095 mmol), tris(dibenzylideneacetone)dipalladium (0.058 g, 0.063 mmol), ethyl 5-bromo-8-cyano-9H-carbazole-2-carboxylate (0.85 g, 2.105 mmol) and (R)-benzyl piperidin-3-ylcarbamate (0.493 g, 2.105 mmol) was suspended in 1,4-dioxane (70 mL). The mixture was purged with nitrogen and heated at 100° C. for 18 h. The mixture was cooled to rt and concentrated. The residue was partitioned between EtOAc and NaHCO3 (aq). The organic phase was washed with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 80:20 to 60:40 hexane-EtOAc) to provide (R)-ethyl 5-(3-(benzyloxycarbonylamino)piperidin-1-yl)-8-cyano-9H-carbazole-2-carboxylate as a brown solid (0.68 g, 70% purity, 37% yield), used without further purification. Mass spectrum m/z 497.2 (M+H)+.

Workup

  1. customThe mixture was purged with nitrogen
  2. temperatureThe mixture was cooled to rt
  3. concentrationconcentrated
  4. customThe residue was partitioned between EtOAc and NaHCO3 (aq)
  5. washThe organic phase was washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (
  9. washeluting with a gradient from 80:20 to 60:40 hexane-EtOAc)

Sources & evidence

ORD record
ord-64bbf0d5d44a4fc796786a3146cc0022
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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