Réaction #218071

Équation de réaction

cyclopentene oxide

tyramine

→

title compound

4-[2-(2-Hydroxycyclopentylamino)ethyl]phenol

Solvants

EtOAc

NaOH

Conditions de réaction

Traitement

1. 1
   workup.WAITat 100° C. for 18 hours
2. 2
   AutreQuench
3. 3
   Autrethe reaction with saturated aqueous NH4Cl (40 mL)
4. 4
   AutreSeparate the layers
5. 5
   workup.STIRRINGafter shaking
6. 6
   LavageWash the organic layer with H2O and brine (50 mL each)
7. 7
   ExtractionBack-extract the aqueous layers with CH2Cl2, EtOAc and CH2Cl2 (50 mL each)
8. 8
   Concentrationconcentrate
9. 9
   Autredecant off the supernatant
10. 10
    workup.DISSOLUTIONDissolve the residual solid in H2O
11. 11
    Extractionextract it with 10:40:50 2.0 M NH3 in MeOH/CH2Cl2/EtOAc (100 mL) and 10:90 2.0 M NH3 in MeOH/CH2Cl2
12. 12
    Concentrationconcentrate
13. 13
    workup.DISSOLUTIONDissolve the residue in a small amount of MeOH
14. 14
    Autrepurify by flash chromatography
15. 15
    Lavageeluting with 10:40:50 2.0 M NH3 in MeOH/CH2CL2/EtOAc

Mode opératoire

Stir a mixture of cyclopentene oxide (482.0 mg, 5.73 mmol) and tyramine (943.2 mg, 6.88 mmol) in 1.0 N NaOH (20 mL) at room temperature for 64 hours, at 45-55° C. for 6 hours, and at 100° C. for 18 hours. Quench the reaction with saturated aqueous NH4Cl (40 mL) and take it up in EtOAc (50 mL). Separate the layers after shaking. Wash the organic layer with H2O and brine (50 mL each). Back-extract the aqueous layers with CH2Cl2, EtOAc and CH2Cl2 (50 mL each). Adjust the pH of the combined aqueous layers to alkaline and concentrate. Suspend the residue in 10:40:50 2.0 M NH3 in MeOH/CH2Cl2/EtOAc and decant off the supernatant. Dissolve the residual solid in H2O and extract it with 10:40:50 2.0 M NH3 in MeOH/CH2Cl2/EtOAc (100 mL) and 10:90 2.0 M NH3 in MeOH/CH2Cl2. Combine all the organic layers and concentrate. Dissolve the residue in a small amount of MeOH and purify by flash chromatography, eluting with 10:40:50 2.0 M NH3 in MeOH/CH2CL2/EtOAc to afford the title compound as a 1:3 cis/trans isomeric mixture (566 mg, 45%): MS ES+ 222.0 (M+H)+, HPLC [YMC-Pack Pro C-18 (150×4.6 min, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 5-95% over 19 min], tR=4.72 min, 76% and 6.52 min, 24%.

Source