Cesium carbonate → HCID 178472425, compound

HRID 518633Notes

Reaction equation

HRID 518633 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([OH:17])=[O:16])[CH2:11][CH2:10]2)[C:5]([N+:18]([O-:20])=[O:19])=[CH:4][N:3]=1.[CH2:21]([O:28][CH2:29][CH2:30][OH:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:38]1OCCOCCOCCOCCOCCO[CH2:39]1.S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH2:21]([O:28][CH2:29][CH2:30][O:31][C:2]1[CH:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([O:17][CH2:38][CH3:39])=[O:16])[CH2:11][CH2:10]2)[C:5]([N+:18]([O-:20])=[O:19])=[CH:4][N:3]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 121412-(Benzyloxy) ethanolHCID 24386Thionyl ChlorideHCID 2855718-Crown-6HCID 178525752HCID 178525752, compound

Product 1

HCID 178472425HCID 178472425, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

To a suspension of cis-4-(2-chloro-5-nitropyridin-4-ylamino)cyclohexanecarboxylic acid (5 g, 16.68 mmol) in toluene (111 mL) was added 2-(benzyloxy)ethanol (7.62 g, 50.0 mmol), cesium carbonate (16.31 g, 50.0 mmol), and 18-crown-6 (6.61 g, 25.02 mmol). The resulting mixture was purged with argon and stirred at 75° C. overnight. The mixture was allowed to cool to RT and diluted with EtOAc to about 150 mL total volume and washed sequentially with brine (2-150 mL), aqueous NH4Cl (2-150 mL) and water (150 mL). The organic phase was collected, dried over sodium sulfate and concentrated under reduced pressure. The residue was suspended in EtOH (111 mL) and thionyl chloride (36.5 mL, 500 mmol) was added dropwise via syringe. The reaction mixture was stirred at RT for 16 hours. The mixture was concentrated to ⅓ volume and diluted with DCM (150 mL). The organic portion was washed with aqueous NaHCO3 (100 mL), dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (10-50% EtOAc/Hexanes) to afford cis-ethyl 4-(2-(2-(benzyloxy)ethoxy)-5-nitropyridin-4-ylamino)cyclohexanecarboxylate (5.6 g, 76% yield). MS m/z=444.2 [M+H]. Calc'd for C23H29N3O6: 443.2.

Workup

  1. customThe resulting mixture was purged with argon
  2. temperatureto cool to RT
  3. additiondiluted with EtOAc to about 150 mL total volume
  4. washwashed sequentially with brine (2-150 mL), aqueous NH4Cl (2-150 mL) and water (150 mL)
  5. customThe organic phase was collected
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. stirringThe reaction mixture was stirred at RT for 16 hours
  9. concentrationThe mixture was concentrated
  10. additiondiluted with DCM (150 mL)
  11. washThe organic portion was washed with aqueous NaHCO3 (100 mL)
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel chromatography (10-50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-515aad16511f4b0c88e936056505780b
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

Loading…