Reaktion #87121

Reaktionsgleichung

cyclopent-1-en-1-yl trifluoromethanesulfonate

TMSCl

(R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate

→

(S)-Methyl 2-(tert-butoxycarbonylamino)-3-cyclopentenylpropanoate

Ausbeute 72.0%

Lösungsmittel

DMF

Brine

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe upper clear liquid was removed
2. 2
   Waschenthe residue was washed with DMF (200 mL×2)
3. 3
   Temperaturthe mixture was cooled to 0° C
4. 4
   workup.STIRRINGThe mixture was stirred at 0° C. under nitrogen for 20 min
5. 5
   SonstigeThe upper clear liquid was removed
6. 6
   workup.ADDITIONAfter addition
7. 7
   workup.STIRRINGthe reaction mixture was stirred at 50° C. under nitrogen overnight
8. 8
   Temperaturthen cooled to ambient temperature
9. 9
   Extraktionthe resulting mixture was extracted with MTBE (300 mL×3)
10. 10
    Waschenwashed with brine
11. 11
    Einengenconcentrated
12. 12
    SonstigeThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=100:1 to 40:1)

Vorschrift

To a suspension of zinc (123 g, 1.90 mol) in DMF (500 mL) was added TMSCl (46 mL) dropwise. The mixture was stirred at ambient temperature for 45 min. The upper clear liquid was removed and the residue was washed with DMF (200 mL×2). The resulting solid was re-suspended in DMF (200 mL) and the mixture was cooled to 0° C. A solution of (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (104 g, 0.320 mol) in DMF (300 mL) was added. The mixture was stirred at 0° C. under nitrogen for 20 min. The upper clear liquid was removed and added to a solution of cyclopent-1-en-1-yl trifluoromethanesulfonate (90 g, 0.37 mol) and Pd(dppf)Cl2 (3.9 g, 4.7 mmol) in DMF (500 mL) dropwise. After addition, the reaction mixture was stirred at 50° C. under nitrogen overnight then cooled to ambient temperature. Brine (500 mL) was added and the resulting mixture was extracted with MTBE (300 mL×3). The organics were combined, washed with brine, and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=100:1 to 40:1) to afford (S)-Methyl 2-(tert-butoxycarbonylamino)-3-cyclopentenylpropanoate as viscous oil (62 g, 72% yield). 1H NMR (300 MHz, CDCl3): δ 5.48 (br s, 1H), 4.97 (d, J=6.6 Hz, 1H), 4.40-4.43 (m, 1H), 3.74 (s, 3H), 2.46-2.63 (m, 2H), 2.23-2.34 (m, 4H), 1.82-1.93 (m, 2H), 1.45 (s, 9H).

Quelle