Reaction #657300

Reaction equation

DMF

HATU

DIPEA

crude compound 4

2-(1-Ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-hydroxy-cyclopentane carboxylic acid diisopropylethylamine salt

→

compound 6

Yield 74.0%

1-{[2-(Hex-5-enylmethylcarbamoyl)-4-hydroxycyclopentane carbonyl]amino}-2-vinylcyclopropane carboxylic acid ethyl ester

Yield 74.0%

Solvents

DCM

Conditions

Workup

1. 1
   Concentrationthe reaction mixture was concentrated in vacuo
2. 2
   workup.DISSOLUTIONThe residue was re-dissolved in EtOAc (100 mL)
3. 3
   Washthe organic phase washed with 0.1 M HCl (aq), K2CO3 (aq) and brine
4. 4
   Dryingdried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   OtherEvaporation of the solvent in vacuo
7. 7
   Othergave an oil which
8. 8
   Otherwas purified by flash chromatography (Silica, EtOAc:MeOH)

Procedure

The crude compound 4 (5.5 mmol) was dissolved in DCM (50 mL) and DMF (14 mL) followed by addition of HATU (2.09 g, 5.5 mmol), 5 (678 mg, 6.0 mmol) and DIPEA (3.08 mL, 17.5 mmol) at room temperature. The reaction was stirred at ambient temperature for 1 h. LC/MS analysis showed complete conversion and the reaction mixture was concentrated in vacuo. The residue was re-dissolved in EtOAc (100 mL) and the organic phase washed with 0.1 M HCl (aq), K2CO3 (aq) and brine, dried (MgSO4) and filtered. Evaporation of the solvent in vacuo gave an oil which was purified by flash chromatography (Silica, EtOAc:MeOH) to afford the target compound 6 (1.65 g, 74%). TLC (Silica): MeOH:EtOAc 5:95, Rf=0.5; LC/MS (Method A): tR=3.44 min, >95%, m/z (ESI+)=407 (MH+).

Source