Cesium carbonate → HCID 66800129, compound

HRID 1057149Notes

Reaction equation

HRID 1057149 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][CH:3]=1.[CH3:9][C@@H:10]1[CH2:14][CH2:13][N:12]([C@@H:15]([CH3:18])[CH2:16][OH:17])[CH2:11]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)CCC.[Cu]I>[I:8][C:5]1[CH:6]=[CH:7][C:2]([O:17][CH2:16][C@@H:15]([N:12]2[CH2:13][CH2:14][C@@H:10]([CH3:9])[CH2:11]2)[CH3:18])=[CH:3][CH:4]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 12208p-DiiodobenzeneHCID 58743044HCID 58743044, compound

Product 1

HCID 66800129HCID 66800129, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8008ButyronitrileSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 1,4-diiodobenzene (2.07 g, 6.27 mmol), ((S)-2-((R)-3-methylpyrrolidin-1-yl)propan-1-ol (0.6 g, 4.18 mmol), CuI (80 mg, 0.4 mmol), cesium carbonate (1.36 g, 4.18 mmol) in butyronitrile (4 mL) was degassed and then heated at 125° C. overnight. The mixture was cooled to room temperature, filtered through celite and washed with EtOAc. The filtrate was concentrated and purified on a silica gel column using 0-10% methanol in dichloromethane to afford (R)-1-((S)-1-(4-iodophenoxy)propan-2-yl)-3-methylpyrrolidine (1.1 g, 78%). 1H NMR (400 MHz, DMSO-d6) δ: 7.57 (d, 2H), 6.79 (d, 2H), 4.04-3.99 (m, 1H), 3.89-3.78 (m, 1H), 2.94-2.85 (m, 1H), 2.66-2.56 (m, 2H), 2.56 (m, 1H), 2.15-2.05 (m, 2H), 1.90-1.86 (m, 1H), 1.24-1.22 (m, 1H), 1.10 (d, 3H), 0.96 (d, 3H). LCMS: 346 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered through celite
  3. washwashed with EtOAc
  4. concentrationThe filtrate was concentrated
  5. custompurified on a silica gel column

Sources & evidence

ORD record
ord-c4649ee84971453285077adadc8ca07f
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

Loading…