Cesium carbonate → HCID 178490342, compound

HRID 492494

Reaction equation

HRID 492494 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1>CN(C=O)C>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][CH2:16][NH:1][C@H:2]2[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 875134-(2-Chloroethyl)phenyl methyl etherHCID 178511715HCID 178511715, compound

Product 1

HCID 178490342HCID 178490342, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Heat a mixture of (±)-(trans)-4-aminocyclohexanol (607 m, 5.3 mmol), Cs2CO3 (4.300 g, 13.2 mmol), and 1-(2-chloroethyl)-4-methoxybenzene (0.8 mL) in DMF (10 mL) at 100° C. for 19 hours. Quench the reaction with saturated aqueous NH4Cl (40 mL). Adjust the pH to alkaline and concentrate to dryness. Suspend the residue in 50:40:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH and stir vigorously for 1 hour. Decant the supernatant. Suspend the residue in 10:90 2.0 M NH3 in MeOH/CH2Cl2 for 30 minutes and filter. Combine the organic layers, concentrate, and purify by flash chromatography, eluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH to afford the title compound (258.3 mg, 20%): MS ES+ 250.0 (M+H)+, HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=1.96 min, 100% purity.

Workup

  1. temperatureHeat
  2. customQuench
  3. customthe reaction with saturated aqueous NH4Cl (40 mL)
  4. concentrationconcentrate to dryness
  5. customDecant the supernatant
  6. customfor 30 minutes
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify by flash chromatography
  10. washeluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH

Sources & evidence

ORD record
ord-5937840d53af42e0a2103d373c867d66
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Linked notes

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