Cesium carbonate → HCID 86685932, compound

HRID 2277605Notes

Reaction equation

HRID 2277605 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[N:6][CH:7]=1.[Cl:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[C:16](=[O:20])[NH:15][C:14]2([CH3:22])[CH3:21].C([O-])([O-])=O.[Cs+].[Cs+].N[C@H]1CCCC[C@@H]1N>O1CCOCC1.[Cu]I.O>[Cl:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[C:16](=[O:20])[N:15]([C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH2:8][OH:9])[CH:3]=1)[C:14]2([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 4793071,2-Diaminocyclohexane, (+)-HCID 2784733(5-Bromo-3-pyridinyl)methanolHCID 71743949HCID 71743949, compound

Product 1

HCID 86685932HCID 86685932, compoundYield 90.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

In a 25-mL sealed tube, (5-bromo-pyridin-3-yl)-methanol (900 mg, 4.8 mmol), 5-chloro-3,3-dimethyl-2,3-dihydro-isoindol-1-one (intermediate A-12 [C], 858 mg, 4.4 mmol), CuI (200 mg, 1.1 mmol), Cs2CO3 (3.0 g, 9.2 mmol) and (+)-(S,S)-1,2-diaminocyclohexane (0.4 mL, 3.2 mmol) were dissolved in dioxane (8.0 mL). The resulting reaction mixture was heated at 150° C. for 3 hours before it was poured into H2O (50 mL) and extracted with EtOAc (2×125 mL). The organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was purified by silica gel flash chromatography (30-100% EtOAc-hexane gradient) to yield the title compound (1.2 g, 90%) as a light yellow solid. MS: 303.2 (M+H+).

Workup

  1. customIn a 25-mL sealed tube
  2. customThe resulting reaction mixture
  3. extractionextracted with EtOAc (2×125 mL)
  4. washThe organic layer was washed with brine
  5. customdried over anhy
  6. filtrationNa2SO4, filtered
  7. concentrationconcentrated in vacuo
  8. customto give a crude product which
  9. customwas purified by silica gel flash chromatography (30-100% EtOAc-hexane gradient)

Sources & evidence

ORD record
ord-378a07984f084802912d06ed6197c0c1
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

Loading…